Artemisinin Cancer Research Results

ART/DHA, Artemisinin: Click to Expand ⟱
Features:

Artemisinin — a plant-derived sesquiterpene lactone endoperoxide (from Artemisia annua) best known as the parent scaffold for artemisinin-class antimalarials and widely investigated as a tumor-selective redox/iron-reactive cytotoxic agent. It is a small-molecule natural product (drug-like phytochemical) whose major clinical derivatives include artesunate (water-soluble), artemether/arteether (lipophilic), and the active metabolite dihydroartemisinin (DHA). In oncology literature the abbreviation set commonly includes ART (artemisinin), AS (artesunate), and DHA (dihydroartemisinin); many mechanistic claims are derivative-specific and exposure/iron-context dependent.

Primary mechanisms (ranked):

  1. Iron-dependent activation of the endoperoxide bridge causing ROS/lipid peroxidation stress and tumor-selective cytotoxicity (iron-high contexts)
  2. Ferroptosis sensitization/induction via iron handling and lipid peroxidation programs (often linked to ferritin/lysosome biology; context-dependent)
  3. Mitochondrial dysfunction with ΔΨm loss and intrinsic apoptosis signaling (downstream of oxidative stress)
  4. ER stress / UPR activation (stress-amplification axis)
  5. Hypoxia–metabolism suppression (HIF-1α and glycolysis program attenuation; model-dependent)
  6. Pro-survival inflammatory signaling suppression (e.g., NF-κB / STAT3 axes; model-dependent)

Bioavailability / PK relevance: Oral artemisinin has variable and generally limited systemic exposure with a short half-life on the order of hours; many anticancer in-vitro concentrations exceed typical achievable free-plasma levels without formulation strategies. Artesunate is rapidly converted to DHA; in an FDA label dataset (IV artesunate for severe malaria), artesunate has a very short half-life (~0.3 h) and DHA ~1.3 h, emphasizing exposure-time constraints and the need to interpret “ART/AS/DHA” PK separately.

In-vitro vs systemic exposure relevance: Many reported anticancer effects are driven by oxidative stress at micromolar in-vitro conditions and may be difficult to reproduce systemically without targeted delivery, local administration, or combination strategies that increase intratumoral iron/ROS burden (context-dependent).

Clinical evidence status: Cancer use remains investigational (preclinical-dominant with small/early human studies). Multiple registered clinical studies have evaluated artesunate/derivatives in oncology settings (e.g., phase I solid tumor IV artesunate; small/phase II-style neoadjuvant/adjunct trials), but there is no major regulatory approval for cancer indications; artesunate is approved/used clinically for severe malaria.

Artemisinin a compound in a Chinese herb that may inhibit tumor growth and metastasis Artemisinin (antimalarial drugs)
Artesunic acid (Artesunate) , Dihydroartemisinin (DHA), artesunate, arteether, and artemether, SM735, SM905, SM933, SM934, and SM1044

The induction of OS in tumor cells via the production of ROS is the key mechanism of ART against cancer.
combination of ART and Nrf2 inhibitors to promote ferroptosis may have more efficient anticancer effects without damaging normal cells.

Summary:
- One of the strongest tumor-selective pro-oxidants, mechanism related with iron. Synergizes with iron-rich tumors
-ROS seems to affect both cancer and normal cells
- Delivery of artemisinin in conjugate form with transferrin or holotransferrin (serum iron transport proteins) have been shown to greatly improve its effectiveness.
- Potential direct inhibitor of STAT3
- Artemisinin synergized with the glycolysis inhibitor 2DG (2-deoxy- D -glucose)
ART Combined Therapy: Allicin, Resveratrol, Curcumin, VitC (but not orally at same time), Butyrate , 2-DG, Aminolevulinic AcidG
-possible problems with liver toxicity??

-Artesunate (ART), an artemisinin compound, is known for lysosomal degradation of ferritin, inducing oxidative stress and promoting cancer cell death.

Pathways:
- Increasing reactive oxygen species (ROS) production. This oxidative stress can cause the loss of mitochondrial membrane potential, leading to cytochrome c release and subsequent activation of caspase cascades.
- Downregulate HIF-1α
- By impairing glycolysis, artemisinin might force cells to rely on oxidative phosphorylation (OXPHOS) for energy production.
- Inhibit GLUT1 (glucose uptake), HK2, PKM2 (slow the glycolytic flux, thereby reducing the energy supply)
- Minimal NRF2 activation

-Artemisinin has a half-life of about 3-4 hours, Artesunate 40 minutes and Artemether 12 hours. Peak plasma levels occur in 1-2 hour.
BioAv 21%, poor-good solubility. Artesunate (ART), a water soluble derivative of artemisinin. concentrations higher in blood, colon, liver, kidney (highly perfused organs)
Pathways:
- induce ROS production, iron dependent (affect both cancer and normal cells)
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓,
- Both Lowers (and raises) AntiOxidant defense in Cancer Cells: NRF2↓(contary), SOD↓, GSH↓ Catalase↓ GPx↓
- Small evidence of Raising AntiOxidant defense in Normal Cells: ROS↓(contary), NRF2↑, SOD↑(contary), GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : NLRP3↓, TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, TIMP2, IGF-1↓, uPA↓, VEGF↓, ROCK1↓, NF-κB↓, TGF-β↓, ERK↓
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓, ERK↓, EMT↓, TOP1↓,
- inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, ECAR↓, GRP78↑, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, EGFR↓, Integrins↓,
- some small indication of inhibiting Cancer Stem Cells : CSC↓, Hh↓, β-catenin↓, sox2↓, OCT4↓,
- Others: PI3K↓, AKT↓, JAK">JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK, ERK↓, JNK,
- Synergies: chemo-sensitization, RadioSensitizer, Others(review target notes),

- Selectivity: Cancer Cells vs Normal Cells
Often synergistic with ROS-based chemo

Artemisinin-class (ART/AS/DHA) mechanisms relevant to cancer biology

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 Iron-activated endoperoxide chemistry and ROS burden ROS↑, lipid peroxidation↑, macromolecular damage↑ (iron-high contexts) ROS↔ to ↑ (dose-dependent) P Pro-oxidant, tumor-biased cytotoxic stress Core premise: iron availability (labile iron pool, heme/Fe²⁺ context) gates potency and selectivity; derivative and formulation matter.
2 Ferroptosis susceptibility Ferroptosis↑ (context-dependent), lipid-ROS↑ Ferroptosis↔ (context-dependent) R Non-apoptotic death program engagement or sensitization Evidence supports artemisinin-compounds as ferroptosis sensitizers/inducers in multiple models; often tied to iron handling and lipid peroxidation control nodes.
3 Ferritin and lysosome axis Ferritin turnover↑ / lysosomal iron↑ (model-dependent) → ROS↑ ↔ (model-dependent) R Iron mobilization that amplifies oxidative injury DHA/derivatives have been reported to engage ferritin/lysosome-related processes that increase reactive iron, supporting ferroptotic and apoptotic stress amplification.
4 Mitochondria and MPTP ΔΨm↓, mitochondrial ROS↑, Cyt-c release↑, apoptosis↑ Stress responses↔ to ↑ (dose-dependent) R Intrinsic apoptosis downstream of redox injury Mitochondrial impairment is commonly reported as a downstream execution route after ROS/iron activation; can intersect with ferroptosis via redox spillover.
5 ER stress and UPR ER stress↑, UPR↑ ↔ to ↑ (stress-dose dependent) R Proteostasis collapse / stress signaling Often co-occurs with ROS-driven injury; may contribute to growth arrest and death pathway crosstalk.
6 HIF-1α axis HIF-1α↓ (model-dependent) ↔ G Anti-hypoxic adaptation Reported suppression of hypoxia programs may reduce angiogenic and glycolytic adaptation in some tumors.
7 Glycolysis and glucose transport Glycolysis↓, GLUT1/HK2/PKM2↓ (model-dependent) ↔ (context-dependent) G Metabolic constraint Metabolic effects vary by cell state; can synergize with glycolysis inhibitors in model systems.
8 STAT3 axis STAT3↓ (model-dependent) ↔ G Pro-survival transcriptional attenuation Reported in subsets of studies; may contribute to reduced proliferation/survival signaling.
9 NF-κB and inflammatory signaling NF-κB↓, inflammatory cytokine programs↓ (model-dependent) Inflammation↓ (context-dependent) G Anti-inflammatory / pro-differentiation pressure Can be beneficial for tumor microenvironment modulation, but directionality and net effect depend on immune context.
10 NRF2 axis NRF2↔ (model-dependent; adaptive resistance possible) NRF2↔ to ↑ (context-dependent) G Redox adaptation gatekeeper NRF2 status can determine sensitivity vs resistance to ROS/ferroptosis; combinations that blunt NRF2 defenses are often proposed experimentally.
11 Clinical Translation Constraint Short exposure window; achievable concentrations may be below many in-vitro active ranges; heterogeneity in iron/redox state; derivative-specific PK Off-target oxidative stress risk (dose/formulation dependent) G Limits systemic reproducibility Interpret ART vs AS vs DHA separately; artesunate→DHA conversion is rapid and half-lives are short (route-dependent). Targeted delivery and combination strategies are common translational approaches.

TSF legend: P: 0–30 min    R: 30 min–3 hr    G: >3 hr
Scientific Papers found: Click to Expand⟱
4438- AgNPs,  ART/DHA,    Biogenic synthesis of AgNPs using Artemisia oliveriana extract and their biological activities for an effective treatment of lung cancer
- in-vitro, Lung, A549
EPR↑, cellular uptake of the AgNPs results indicated that the AgNPs accumulated within the cell.
BAX↑, Bax, Bcl-2, caspase-3 (CASP3), caspase-9 (CASP9)
Bcl-2↑,
Casp3↑,
Casp9↑,
DNAdam↑, apoptotic effects of the AgNPs through DNA fragmentation test, flow cytometry and cell cycle analysis indicated the induction of apoptosis in the A549 cell line.
TumCCA↑,
Apoptosis↑,

4552- AgNPs,  ART/DHA,    Green synthesis of silver nanoparticles using Artemisia turcomanica leaf extract and the study of anti-cancer effect and apoptosis induction on gastric cancer cell line (AGS)
- in-vitro, GC, AGS
AntiCan↑, iologically synthesized silver nanoparticles induced apoptosis, and showed a cytotoxic and anti-cancer effect against gastric cancer cell lines in a dose- and time-dependent manner.
Apoptosis↑,
eff↑, Biologically synthesized nanoparticles may possess higher anti-cancer properties than commercial silver

3388- ART/DHA,    Keap1 Cystenine 151 as a Potential Target for Artemisitene-Induced Nrf2 Activation
- in-vitro, Lung, A549 - in-vitro, Nor, GP-293 - in-vitro, BC, MDA-MB-231
NRF2↑, ATT upregulated Nrf2 in the MB231 cells . ATT increased Nrf2 levels at low doses ranging from 1 to 5 μM
ROS∅, ATT does not increase ROS production and cannot active Nrf2 by inducing oxidative stress

3666- ART/DHA,    Artemisinin Attenuates Amyloid-Induced Brain Inflammation and Memory Impairments by Modulating TLR4/NF-κB Signaling
- NA, AD, NA
*Inflam↓, Artemisinin has potent anti-inflammatory and immune activities.
*neuroP↑, Artemisinin inhibited neuroinflammation and exerted neuroprotective effects by regulating the Toll-like receptor 4 (TLR4)/Nuclear factor-kappa B (NF-κB) signaling pathway.
*TLR4↓,
*NF-kB↓,
*memory↑, reversing spatial learning and memory deficits.
*ROS↓, Artemisinin Decreased the Production of ROS and iNOS in BV2 Cells
*iNOS↓,
*COX2↓, Artemisinin treatment decreased the expression of COX2 and iNOS
*cognitive↑, Artemisinin Improved the Cognitive Impairment of AD Model Mice

3665- ART/DHA,    Artemisinin B Improves Learning and Memory Impairment in AD Dementia Mice by Suppressing Neuroinflammation
- Review, AD, NA
*Inflam↓, artemisinin B from Artemisia annua Linn. has strong anti-inflammatory and immunological activities.
*NO↓, artemisinin B inhibited NO secretion from LPS-induced BV2 cells and significantly reduced the expression levels of the inflammatory cytokines IL-1β, IL-6 and TNF-α.
*IL1β↓,
*IL6↓,
*TNF-α↓,
*MyD88↓, accompanied by reduced gene expression levels of MyD88 and NF-κB as well as TLR4 and MyD88 protein levels
*NF-kB↓,
*TLR4↓,
*memory↑, artemisinin B improved spatial memory in dementia mice in the water maze and step-through tests

3396- ART/DHA,    Progress on the study of the anticancer effects of artesunate
- Review, Var, NA
TumCP↓, reported inhibitory effects on cancer cell proliferation, invasion and migration.
TumCI↓,
TumCMig↓,
Apoptosis↑, ART has been reported to induce apoptosis, differentiation and autophagy in colorectal cancer cells by impairing angiogenesis
Diff↑,
TumAuto↑,
angioG↓,
TumCCA↑, inducing cell cycle arrest (11), upregulating ROS levels, regulating signal transduction [for example, activating the AMPK-mTOR-Unc-51-like autophagy activating kinase (ULK1) pathway in human bladder cancer cells]
ROS↑,
AMPK↑,
mTOR↑,
ChemoSen↑, ART has been shown to restore the sensitivity of a number of cancer types to chemotherapeutic drugs by modulating various signaling pathways
Tf↑, ART could upregulate the mRNA levels of transferrin receptor (a positive regulator of ferroptosis), thus inducing apoptosis and ferroptosis in A549 non-small cell lung cancer (NSCLC) cells.
Ferroptosis↑,
Ferritin↓, ferritin degradation, lipid peroxidation and ferroptosis
lipid-P↑,
CDK1↑, Cyclin-dependent kinase 1, 2, 4 and 6
CDK2↑,
CDK4↑,
CDK6↑,
SIRT1↑, Sirt1 levels
COX2↓,
IL1β↓, IL-1? ?
survivin↓, ART can selectively downregulate the expression of survivin and induce the DNA damage response in glial cells to increase cell apoptosis and cell cycle arrest, resulting in increased sensitivity to radiotherapy
DNAdam↑,
RadioS↑,

3395- ART/DHA,    Artesunate Induces Ferroptosis in Hepatic Stellate Cells and Alleviates Liver Fibrosis via the ROCK1/ATF3 Axis
- in-vitro, NA, HSC-T6
*Ferroptosis↑, Art induced ferroptosis in HSCs following glutathione-dependent antioxidant system inactivation resulting from nuclear accumulation of unphosphorylated ATF3 mediated by ROCK1-ubiquitination in vitro
*GSH↓,
*ROCK1↓, Interestingly, the ROCK1 protein level was significantly reduced after Art treatment compared with ROCK2, which raised the probability that ROCK1 was involved in the regulation of ferroptosis in LX2 cells

3394- ART/DHA,    Anticancer activities and mechanisms of heat-clearing and detoxicating traditional Chinese herbal medicine
IGF-1R↓, Artemisinin downregulated IGF-IR expression and inhibited the growth of MCF-7 breast tumor cell xenografts in nude mice

3393- ART/DHA,    Artemisinin-derived artemisitene blocks ROS-mediated NLRP3 inflammasome and alleviates ulcerative colitis
- in-vivo, Col, NA
*ROS↓, Artemisitene inhibits ROS (especially mtROS) production and NLRP3 inflammasome assembly.
*NLRP3↓,
*Inflam↓, artemisitene significantly attenuated inflammatory response in DSS-induced ulcerative colitis

3392- ART/DHA,    Artemisinin inhibits inflammatory response via regulating NF-κB and MAPK signaling pathways
- in-vitro, Nor, Hep3B - in-vivo, NA, NA
*Inflam↓, anti-inflammatory effects of artemisinin in TPA-induced skin inflammation in mice.
*NF-kB↓, artemisinin significantly inhibited the expression of NF-?B reporter gene induced by TNF-? in a dose-dependent manner
*ROS↓, artemisinin significantly impaired the ROS production and phosphorylation of p38 and ERK,
*p‑p38↓,
*p‑ERK↓,

3391- ART/DHA,    Antitumor Activity of Artemisinin and Its Derivatives: From a Well-Known Antimalarial Agent to a Potential Anticancer Drug
- Review, Var, NA
TumCP↓, inhibiting cancer proliferation, metastasis, and angiogenesis.
TumMeta↓,
angioG↓,
TumVol↓, reduces tumor volume and progression
BioAv↓, artemisinin has low solubility in water or oil, poor bioavailability, and a short half-life in vivo (~2.5 h)
Half-Life↓,
BioAv↑, semisynthetic derivatives of artemisinin such as artesunate, arteeter, artemether, and artemisone have been effectively used as antimalarials with good clinical efficacy and tolerability
eff↑, preloading of cancer cells with iron or iron-saturated holotransferrin (diferric transferrin) triggers artemisinin cytotoxicity
eff↓, Similarly, treatment with desferroxamine (DFO), an iron chelator, renders compounds inactive
ROS↑, ROS generation may contribute with the selective action of artemisinin on cancer cells.
selectivity↑, Tumor cells have enhanced vulnerability to ROS damage as they exhibit lower expression of antioxidant enzymes such as superoxide dismutase, catalase, and gluthatione peroxidase compared to that of normal cells
TumCCA↑, G2/M, decreased survivin
survivin↓,
BAX↑, Increased Bax, activation of caspase 3,8,9 Decreased Bc12, Cdc25B, cyclin B1, NF-κB
Casp3↓,
Casp8↑,
Casp9↑,
CDC25↓,
CycB/CCNB1↓,
NF-kB↓,
cycD1/CCND1↓, decreased cyclin D, E, CDK2-4, E2F1 Increased Cip 1/p21, Kip 1/p27
cycE/CCNE↓,
E2Fs↓,
P21↑,
p27↑,
ADP:ATP↑, Increased poly ADP-ribose polymerase Decreased MDM2
MDM2↓,
VEGF↓, Decreased VEGF
IL8↓, Decreased NF-κB DNA binding [74, 76] IL-8, COX2, MMP9
COX2↓,
MMP9↓,
ER Stress↓, ER stress, degradation of c-MYC
cMyc↓,
GRP78/BiP↑, Increased GRP78
DNAdam↑, DNA damage
AP-1↓, Decreased NF-κB, AP-1, Decreased activation of MMP2, MMP9, Decreased PKC α/Raf/ERK and JNK
MMP2↓,
PKCδ↓,
Raf↓,
ERK↓,
JNK↓,
PCNA↓, G2, decreased PCNA, cyclin B1, D1, E1 [82] CDK2-4, E2F1, DNA-PK, DNA-topo1, JNK VEGF
CDK2↓,
CDK4↓,
TOP2↓, Inhibition of topoisomerase II a
uPA↓, Decreased MMP2, transactivation of AP-1 [56, 88] NF-κB uPA promoter [88] MMP7
MMP7↓,
TIMP2↑, Increased TIMP2, Cdc42, E cadherin
Cdc42↑,
E-cadherin↑,

3390- ART/DHA,    Ferroptosis: The Silver Lining of Cancer Therapy
Ferroptosis↑, Artesunate induces ferroptosis in tumour cells by enhancing lysosomal activity and increasing lysosomal iron concentration
Iron↑,
NCOA4↝, Artesunate regulates ferroptosis by promoting ferritinophagy by regulating the gene expression of NCOA4, which leads to an increase in the iron levels
ROS↑, overproduction of ROS triggered by the Fenton reaction between iron ion and hydrogen peroxide is a crucial factor for inducing ferroptosis.
Fenton↑,
Tf↓, artesunate can induce ferroptosis in Adriamycin-resistant leukaemia cells by decreasing TF levels

3389- ART/DHA,    Emerging mechanisms and applications of ferroptosis in the treatment of resistant cancers
- Review, Var, NA
GSH↓, decreasing cellular GSH levels and the presence of iron-induced ROS generation
ROS↑,
NRF2↑, However, ART-mediated killing of cisplatin-resistant HNC cells can simultaneously activate the NRF2-antioxidant response element (ARE) pathway, which contributes to ferroptosis resistance
eff↑, Therefore, the combination of ART with NRF2 genetic silencing or trigonelline may provide a preferable efficacy

4278- ART/DHA,    Artemisinin Ameliorates the Neurotoxic Effect of 3-Nitropropionic Acid: A Possible Involvement of the ERK/BDNF/Nrf2/HO-1 Signaling Pathway
- in-vivo, NA, NA
*IL6↓, ART effectively suppressed neuroinflammatory (IL-6) and apoptotic markers (caspase 3 and 9), increasing BDNF levels and restoring the p-ERK1/2, Nrf2, and HO-1 expression.
*Casp3↓,
*Casp9↓,
*BDNF↑,
*ERK↑,
*NRF2↑,
*HO-1↑,
*neuroP↑, ART could exert its neuroprotective effect via antioxidant, anti-inflammatory, and antiapoptotic properties with a possible involvement of the ERK/BDNF/Nrf2/HO-1 pathway.
*antiOx↑,
*Inflam↓,

3387- ART/DHA,    Ferroptosis: A New Research Direction of Artemisinin and Its Derivatives in Anti-Cancer Treatment
- Review, Var, NA
BioAv↓, Artemisinin, extracted from Artemisia annua L., is a poorly water-soluble antimalarial drug
lipid-P↑, promote the accumulation of intracellular lipid peroxides to induce cancer cell ferroptosis, alleviating cancer development and resulting in strong anti-cancer effects in vitro and in vivo.
Ferroptosis↑,
Iron↑, Artemisinin and Its Derivatives Upregulate Fe2+ Levels in Cancer Cells
GPx4↓, GPX4-dependent defense system is significantly inhibited
GSH↓, , leading to a significant decrease in GSH, GPX4, and SLC7A11 protein expression
P53↑, ARTEs can upregulate p53 protein expression in multiple cancer cells
ER Stress↑, ARTEs can trigger ERS in cancer cells to activate the PERK-ATF4 pathway and upregulate GRP78 expression
PERK↑,
ATF4↑,
GRP78/BiP↑,
CHOP↑, which activates CHOP
ROS↑, promoting the accumulation of intracellular ROS, and leading to ferroptosis
NRF2↑, ARTEs can activate the nuclear factor erythroid-derived 2-like 2 (Nrf2) -γ-glutamyl-peptide pathway in cancer cells, resulting in cancer cell ferroptosis resistance

3386- ART/DHA,    Effects of Caffeine-Artemisinin Combination on Liver Function and Oxidative Stress in Selected Organs in 7,12-Dimethylbenzanthracene-Treated Rats
- in-vivo, Nor, NA
*MDA↑, Table 1 normal vs art
*SOD↓, Table 2 normal vs art
*GSH∅, Table 3 normal vs art (slight increase)
*Catalase↓, table 4 normal vs art

3385- ART/DHA,    Interaction of artemisinin protects the activity of antioxidant enzyme catalase: A biophysical study
- Study, NA, NA
*NF-kB↑, protective role of derivative of ART was observed in asthma condition where restoration of three fold reduced catalase activity was found by promoting Nuclear factor erythroid-2-related factor (Nrf2)
*Catalase↑,

3384- ART/DHA,    Dihydroartemisinin triggers ferroptosis in primary liver cancer cells by promoting and unfolded protein response‑induced upregulation of CHAC1 expression
- in-vitro, Liver, Hep3B - in-vitro, Liver, HUH7 - in-vitro, Liver, HepG2
Ferroptosis↑, DHA displayed classic features of ferroptosis, such as increased lipid reactive oxygen species
ROS↑,
GSH↓, decreased activity or expression of glutathione (GSH), glutathione peroxidase 4, solute carrier family (SLC) 7 member 11 and SLC family 3 member 2.
UPR↑, DHA activated all three branches of the UPR
GPx4↓, GSH depletion leads to the suppression of glutathione peroxidase (GPX)4, a key glutathione peroxidase known to catalyze the reduction of lipid ROS
PERK↑, DHA was found to activate PERK/eIF2α/ATF4
eIF2α↑,
ATF4↑,

3383- ART/DHA,    Dihydroartemisinin: A Potential Natural Anticancer Drug
- Review, Var, NA
TumCP↓, DHA exerts anticancer effects through various molecular mechanisms, such as inhibiting proliferation, inducing apoptosis, inhibiting tumor metastasis and angiogenesis, promoting immune function, inducing autophagy and endoplasmic reticulum (ER) stres
Apoptosis↑,
TumMeta↓,
angioG↓,
TumAuto↑,
ER Stress↑,
ROS↑, DHA could increase the level of ROS in cells, thereby exerting a cytotoxic effect in cancer cells
Ca+2↑, activation of Ca2+ and p38 was also observed in DHA-induced apoptosis of PC14 lung cancer cells
p38↑,
HSP70/HSPA5↓, down-regulation of heat-shock protein 70 (HSP70) might participate in the apoptosis of PC3 prostate cancer cells induced by DHA
PPARγ↑, DHA inhibited the growth of colon tumor by inducing apoptosis and increasing the expression of peroxisome proliferator-activated receptor γ (PPARγ)
GLUT1↓, DHA was shown to inhibit the activity of glucose transporter-1 (GLUT1) and glycolytic pathway by inhibiting phosphatidyl-inositol-3-kinase (PI3K)/AKT pathway and downregulating the expression of hypoxia inducible factor-1α (HIF-1α)
Glycolysis↓, Inhibited glycolysis
PI3K↓,
Akt↓,
Hif1a↓,
PKM2↓, DHA could inhibit the expression of PKM2 as well as inhibit lactic acid production and glucose uptake, thereby promoting the apoptosis of esophageal cancer cells
lactateProd↓,
GlucoseCon↓,
EMT↓, regulating the EMT-related genes (Slug, ZEB1, ZEB2 and Twist)
Slug↓, Downregulated Slug, ZEB1, ZEB2 and Twist in mRNA level
Zeb1↓,
ZEB2↓,
Twist↓,
Snail?, downregulated the expression of Snail and PI3K/AKT signaling pathway, thereby inhibiting metastasis
CAFs/TAFs↓, DHA suppressed the activation of cancer-associated fibroblasts (CAFs) and mouse cancer-associated fibroblasts (L-929-CAFs) by inhibiting transforming growth factor-β (TGF-β signaling
TGF-β↓,
p‑STAT3↓, blocking the phosphorylation of STAT3 and polarization of M2 macrophages
M2 MC↓,
uPA↓, DHA could inhibit the growth and migration of breast cancer cells by inhibiting the expression of uPA
HH↓, via inhibiting the hedgehog signaling pathway
AXL↓, DHA acted as an Axl inhibitor in prostate cancer, blocking the expression of Axl through the miR-34a/miR-7/JARID2 pathway, thereby inhibiting the proliferation, migration and invasion of prostate cancer cells.
VEGFR2↓, inhibition of VEGFR2-mediated angiogenesis
JNK↑, JNK pathway activated and Beclin 1 expression upregulated.
Beclin-1↑,
GRP78/BiP↑, Glucose regulatory protein 78 (GRP78, an ER stress-related molecule) was upregulated after DHA treatment.
eff↑, results demonstrated that DHA-induced ER stress required iron
eff↑, DHA was used in combination with PDGFRα inhibitors (sunitinib and sorafenib), it could sensitize ovarian cancer cells to PDGFR inhibitors and achieved effective therapeutic efficacy
eff↑, DHA combined with 2DG (a glycolysis inhibitor) synergistically induced apoptosis through both exogenous and endogenous apoptotic pathways
eff↑, histone deacetylase inhibitors (HDACis) enhanced the anti-tumor effect of DHA by inducing apoptosis.
eff↑, DHA enhanced PDT-induced cell growth inhibition and apoptosis, increased the sensitivity of esophageal cancer cells to PDT by inhibiting the NF-κB/HIF-1α/VEGF pathway
eff↑, DHA was added to magnetic nanoparticles (MNP), and the MNP-DHA has shown an effect in the treatment of intractable breast cancer
IL4↓, downregulated IL-4;
DR5↑, Upregulated DR5 in protein, Increased DR5 promoter activity
Cyt‑c↑, Released cytochrome c from the mitochondria to the cytosol
Fas↑, Upregulated fas, FADD, Bax, cleaved-PARP
FADD↑,
cl‑PARP↑,
cycE/CCNE↓, Downregulated Bcl-2, Bcl-xL, procaspase-3, Cyclin E, CDK2 and CDK4
CDK2↓,
CDK4↓,
Mcl-1↓, Downregulated Mcl-1
Ki-67↓, Downregulated Ki-67 and Bcl-2
Bcl-2↓,
CDK6↓, Downregulated of Cyclin E, CDK2, CDK4 and CDK6
VEGF↓, Downregulated VEGF, COX-2 and MMP-9
COX2↓,
MMP9↓,

3382- ART/DHA,    Repurposing Artemisinin and its Derivatives as Anticancer Drugs: A Chance or Challenge?
- Review, Var, NA
AntiCan↑, antimalarial drug, artemisinin that has shown anticancer activities in vitro and in vivo.
toxicity↑, safety of artemisinins in long-term cancer therapy requires further investigation.
Ferroptosis↑, Artemisinins acts against cancer cells via various pathways such as inducing apoptosis (Zhu et al., 2014; Zuo et al., 2014) and ferroptosis via the generation of reactive oxygen species (ROS) (Zhu et al., 2021) and causing cell cycle arrest
ROS↑,
TumCCA↑,
BioAv↝, absolute bioavailability was estimated to be 21.6%. ART has good solubility and is not lipophilic
eff↝, ART would not distribute well to the tissues and might be more effective in treating cancers such as leukemia, hepatocellular carcinoma (HCC), or renal cell carcinoma because the liver and kidney are highly perfused organs.
Half-Life↓, Pharmacokinetic studies showed a relatively short t1/2 of artemisinins. For ART, t1/2 was 0.41 h
Ferritin↓, Figure 3
GPx4↓,
NADPH↓,
GSH↓,
BAX↑,
Cyt‑c↑,
cl‑Casp3↑,
VEGF↓, angiogenesis
IL8↓,
COX2↓,
MMP9↓,
E-cadherin↑,
MMP2↓,
NF-kB↓,
p16↑, cell cycle arrest
CDK4↓,
cycD1/CCND1↓,
p62↓, autophagy
LC3II↑,
EMT↓, suppressing EMT and CSCs
CSCs↓,
Wnt↓, Depress Wnt/β-catenin signaling pathway
β-catenin/ZEB1↓,
uPA↓, Inhibit u-PA activity, protein and mRNA expression
TumAuto↑, Emerging evidence suggests that autophagy induction is one of the molecular mechanisms underlying anticancer activity of artemisinins
angioG↓, Inhibition of Angiogenesis
ChemoSen↑, Many studies also reported that the use of artemisinins sensitized cancer cells to conventional chemotherapy and exerted a synergistic effect on apoptosis, inhibition of cell growth, and a reduction of cell viability, leading to a lower IC50 value

3345- ART/DHA,    Dihydroartemisinin-induced unfolded protein response feedback attenuates ferroptosis via PERK/ATF4/HSPA5 pathway in glioma cells
- in-vitro, GBM, NA
ROS↑, Dihydroartemisinin (DHA) has been shown to exert anticancer activity through iron-dependent reactive oxygen species (ROS) generation, which is similar to ferroptosis, a novel form of cell death
Ferroptosis↑, DHA induced ferroptosis in glioma cells, as characterized by iron-dependent cell death accompanied with ROS generation and lipid peroxidation.
lipid-P↑,
HSP70/HSPA5↑, DHA treatment simultaneously activated a feedback pathway of ferroptosis by increasing the expression of heat shock protein family A (Hsp70) member 5 (HSPA5)
ER Stress↑, DHA caused endoplasmic reticulum (ER) stress in glioma cells, which resulted in the induction of HSPA5 expression by protein kinase R-like ER kinase (PERK)-upregulated activating transcription factor 4 (ATF4)
ATF4↑,
GRP78/BiP↑, HSPA5
MDA↑, DHA significantly increased lipid ROS and MDA levels in glioma cells in a dose- and time-dependent manner.
GSH↓, As an important antioxidant, reduced form GSH was exhausted by DHA
eff↑, Inhibitor of HSPA5 synergistically enhanced anti-tumor effects of DHA
GPx4↑, DHA induced-ER stress in turn activated cell protection against ferroptosis through PERK-ATF4- HSPA5 activation, which promoted the expression of GPX4 to detoxify peroxidized membrane lipids

2582- ART/DHA,  5-ALA,    Mechanistic Investigation of the Specific Anticancer Property of Artemisinin and Its Combination with Aminolevulinic Acid for Enhanced Anticolorectal Cancer Activity
- in-vivo, CRC, HCT116 - in-vitro, CRC, HCT116
eff↑, Guided by this mechanism, the specific cytotoxicity of ART toward CRC cells can be dramatically enhanced with the addition of aminolevulinic acid (ALA), a clinically used heme synthesis precursor, to increase heme levels
ROS↑, We found that artesunate significantly increased ROS levels (Figure 4f) in HCT116 cells
selectivity↑, In contrast, heme levels in normal cells and tissues are strictly controlled and maintained at lower levels, minimizing ART’s activation, which could possibly explain the specificity and low toxicity of ART.
TumCG↓, Strikingly, the combination of artesunate and ALA showed significant tumor growth delay in comparison to both the control and the artesunate or ALA single treatment groups
toxicity↓, Since both artesunate and ALA are clinically used and well-tolerated, (52) this combination has the potential to be safely applied to subsequent clinical testing

2581- ART/DHA,  PB,    Synergistic cytotoxicity of artemisinin and sodium butyrate on human cancer cells
- in-vitro, AML, NA
eff↑, The combination of 20 microM DHA and 1 mM sodium butyrate killed all Molt-4 cells at the 24-hour time-point and did not significantly affect lymphocytes.
selectivity↑,

2580- ART/DHA,  VitC,    Effects of Antioxidants and Pro-oxidants on Cytotoxicity of Dihydroartemisinin to Molt-4 Human Leukemia Cells
- in-vitro, AML, NA
eff↓, Compared to control, ascorbate and H 2 O 2 both caused a significant decrease in cell count both at 24-h (p<0.05 and p<0.0001 for ascorbate and H 2 O 2 , respectively)
other↝, Vitamin C, a common supplement, has been shown to act as both a ROS generator in the presence of iron and copper (15) and as an antioxidant
ROS↑, From our results, we can postulate that ROS generation is causing cell death independently and in combination with DHA
eff↓, Ascorbate can convert ferric iron into ferrous iron (18), the active form that reacts with artemisinin, generating short lived free radicals.
eff↓, If this happens in the stomach of a person who is consuming artemisinin along with ascorbate, ascorbate will convert ferric iron in foods to the ferrous form, which may react with artemisinin locally, making the therapy less effective

555- ART/DHA,    Artemisinin as an anticancer drug: Recent advances in target profiling and mechanisms of action
- Review, NA, NA
STAT3↓, potential direct inhibitor of STAT3

5135- ART/DHA,    Dihydroartemisinin Inhibits mTORC1 Signaling by Activating the AMPK Pathway in Rhabdomyosarcoma Tumor Cells
- vitro+vivo, Var, NA
mTORC1↓, Dihydroartemisinin (DHA), an anti-malarial drug, has been shown to possess potent anticancer activity, partly by inhibiting the mammalian target of rapamycin (mTOR) complex 1 (mTORC1)
AMPK↑, DHA activated AMP-activated protein kinase (AMPK).
TumCG↓, treatment with artesunate, a prodrug of DHA, dose-dependently inhibited tumor growth and concurrently activated AMPK and suppressed mTORC1 in RMS xenografts.

5383- ART/DHA,    Artesunate is a drug used to treat severe malaria.
- Review, Var, NA
Half-Life?, The elimination half life of artesunate is 0.3h with a range of 0.1-1.8h.8 The elimination half life of DHA is 1.3h with a range of 0.9-2.9h.8 Half life after intramuscular administration is 48 min in children and 41 min in adults

5382- ART/DHA,    A phase I study of intravenous artesunate in patients with advanced solid tumor malignancies
- Trial, Var, NA
AntiCan↑, The artemisinin class of anti-malarial drugs has shown significant anti-cancer activity in pre-clinical models.
Dose↝, maximum tolerated dose (MTD) . maximum tolerated dose (MTD) a
Dose↝, MTD of intravenous artesunate is 18 mg/kg

5381- ART/DHA,    Artemisitene triggers calcium-dependent ferroptosis by disrupting the LSH-EWSR1 interaction in colorectal cancer
- in-vitro, CRC, HCT116 - in-vitro, Nor, NCM460 - in-vitro, CRC, HT29 - in-vitro, CRC, HCT8
Ferroptosis↑, Artemisia annua, acted as a CRC therapeutic agent by promoting calcium-dependent ferroptosis.
CYP24A1↓, ATT repressed cytochrome P450 family 24 subfamily A member 1 (CYP24A1) expression, the pivotal mediator of this response
Ca+2↑, ATT downregulated CYP24A1 expression to elevate calcium levels and induce ferroptosis in CRC cells
SCD1↓, The ensuing calcium overload downregulated stearoyl-CoA desaturase (SCD) by CAMKK2/AMPK/SREBF1 axis, enriching oxidizable fatty acids and sensitizing CRC cells to lethal lipid peroxidation.
FAO↑,
lipid-P↑,
eff↑, The results showed that ATT exhibited the highest cytotoxicity, surpassing that of dihydroartemisinin and artesunate, whereas artemisinin and artemether were only weakly effective
selectivity↑, ATT induced cell death in a strictly time-dependent manner and displayed minimal toxicity toward normal NCM460 epithelial cells
other?, Collectively, these data reveal that ATT-driven calcium overload disrupts fatty-acid homeostasis via SCD inhibition, thereby steering CRC cells toward ferroptosis.

5380- ART/DHA,    Artemisinin and Its Derivatives as Potential Anticancer Agents
- Review, Var, NA
TumCG↓, Artemisinin (1, Figure 2) could suppress cell growth [16], reduce angiogenesis-related factors [17], and induce ferroptosis [18] in breast cancer cell lines
angioG↓,
Ferroptosis↑,
TumCP↑, Dihydroartemisinin (2, Figure 2) exhibited anticancer effects against breast cancer by suppressing cell proliferation [16], inhibiting angiogenesis [19], inducing autophagy [20] and pyroptosis [21], and targeting cancer stem cells (CSCs) [
TumAuto↑,
CSCs↑,
eff↑, Dihydroartemisinin is more potent than artemisinin, as the IC50 values at 24 h were lower on MCF-7 (129.1 μM versus 396.6 μM) and MDA-MB-231 (62.95 μM versus 336.63 μM)
YAP/TEAD↓, Additionally, dihydroartemisinin was proven to have the ability to reduce the expression of yes-associated protein 1 (YAP1), which has been commonly used as a prognostic marker in liver cancer.
TumCCA↑, induced G0/G1 cell cycle arrest and apoptosis by promoting oxygen species (ROS) accumulation.
ROS↑,
ChemoSen↑, The application of combination treatment using artemisinin and its derivatives with commonly used chemotherapy drugs, such as cisplatin, carboplatin, doxorubicin, temozolomide, etc., always exhibits significantly improved anticancer effects
N-cadherin↓, and inhibiting the proliferation, colony formation, and invasiveness of colon cancer cells by inhibiting NRP2, N-cadherin, and Vimentin expression
Vim↓,
MMP9↓, by decreasing the expression of HuR and matrix metalloproteinase (MMP)-9 proteins [24],
eff↑, Further investigations suggested that both dihydroartemisinin treatment and the loss of PRIM2 could lead to a decreased GSH level and induce cellular lipid ROS and mitochondrial MDA expression.
STAT3↓, Recently, artemisinin and its derivatives were reported to have potential as direct STAT3 inhibitors [98].
CD133↓, dihydroartemisinin treatment could significantly reduce the expression of CSC markers (CD133, CD44, Nanog, c-Myc, and OCT4) by downregulating Akt/mTOR pathway
CD44↓,
Nanog↓,
cMyc↓,
OCT4↓,
Akt↓,
mTOR↓,

5379- ART/DHA,    Iron-fueled ferroptosis: a new axis for immunomodulation to overcome cancer drug resistance—from immune microenvironment crosstalk to therapeutic translation
Ferritin↓, dihydroartemisinin (DAT, which triggers lysosomal ferritin degradation).
Iron↑, DAT has shown promise in reversing carboplatin resistance in ovarian cancer cell lines by expanding the labile iron pool (LIP) and enhancing Fenton reaction-mediated lipid peroxidation (149).
Fenton↑,
lipid-P↑,
ChemoSen↑, Its advantage lies in synergistic effects with conventional chemotherapies, as iron overload amplifies chemotherapy-induced oxidative stress.
ROS↑,
eff↝, However, DAT requires careful monitoring of systemic iron levels to avoid anemia, and its efficacy is reduced in cancer cells with upregulated ferroportin (an iron export protein).

5378- ART/DHA,    Natural Agents Modulating Ferroptosis in Cancer: Molecular Pathways and Therapeutic Perspectives
- Review, Var, NA
Ferroptosis↑, Artemisinin increases ferroptosis risk in cancer cells by increasing cellular free iron and lipid peroxidation, causing increased membrane permeability and decreased integrity [59]
Iron↑,
lipid-P↑,
MOMP↑,
AntiCan↑, Artemisinin has anticancer and antimalarial properties by upregulating NCOA4 and DMT1 levels, raising ferrous ion levels, and causing ferroptosis by downregulating GSH and GPX4 levels [30, 59, 75].
NCOA4↑,
GSH↓,
GPx4↓,
ROS↑, Artemisinin and its derivatives regulate 20 iron metabolism genes, thereby causing the formation of ROS [76]
ChemoSen↑, Artesunate, when combined with sorafenib, can enhance the susceptibility of hepatocellular carcinoma cells to cisplatin resistance through ferroptosis inhibition [77].
ER Stress↑, artemisinin, specifically ferroptosis, by controlling iron metabolism, producing ROS, and triggering ER‐stress.
DNAdam↑, primary antineoplastic mechanisms of artemisinin are ferroptosis, DNA damage, tumour angiogenesis suppression and cell cycle inhibition [78]
angioG↓,
TumCCA↑,
eff↓, while NAC and ferrostatin‐1 partially reverse these effects [82]

5377- ART/DHA,    Dihydroartemisinin-induced ferroptosis in acute myeloid leukemia: links to iron metabolism and metallothionein
- in-vitro, AML, NA
AntiCan↑, Artemisinin is an anti-malarial drug that has shown anticancer properties
Ferroptosis↑, Recently, ferroptosis was reported to be induced by dihydroartemisinin (DHA) and linked to iron increase.
Iron↑, We found that treatment of DHA induces early ferroptosis by promoting ferritinophagy and subsequent iron increase.
Mets↑, Furthermore, our study demonstrated that DHA activated zinc metabolism signaling, especially the upregulation of metallothionein (MT).
eff↑, Supportingly, we showed that inhibition MT2A and MT1M isoforms enhanced DHA-induced ferroptosis.
GSH↝, Finally, we demonstrated that DHA-induced ferroptosis alters glutathione pool, which is highly dependent on MTs-driven antioxidant response.
eff↑, DHA cooperates with FAC to increase the intracellular iron pool. ferric citrate iron (FAC)
other↓, Under oxidative stress, MT can release Zn2+ (apo-MT) to form thiol groups and participates in GSSG/ GSH reduction.
eff↑, Our current findings also suggest that MT chemical inhibition can cooperate with DHA in primary AML cells in patients.
other↓, Subsequent MT inhibition may sensitize leukemic cells to lipid peroxidation in vitro by impairing GSH regeneration.

5376- ART/DHA,    Artemisinin compounds sensitize cancer cells to ferroptosis by regulating iron homeostasis
- in-vitro, CRC, HCT116 - in-vitro, CRC, HT29 - in-vitro, CRC, SW48 - in-vitro, BC, MDA-MB-453
Ferroptosis↑, artemisinin compounds can sensitize cancer cells to ferroptosis, a new form of programmed cell death driven by iron-dependent lipid peroxidation.
Ferritin↓, Mechanistically, dihydroartemisinin (DAT) can induce lysosomal degradation of ferritin in an autophagy-independent manner, increasing the cellular free iron level and causing cells to become more sensitive to ferroptosis.
Iron↑,
eff↑, we found that DAT can augment GPX4 inhibition-induced ferroptosis
TumAuto↑, DAT sensitizes cells to ferroptosis by stimulating autophagy.
LC3II↑, it caused an increase of LC3-II production
ROS↑, DAT increases lipid ROS and sensitizes cancer cells to ferroptosis

5137- ART/DHA,    Autophagy-dependent cell cycle arrest in esophageal cancer cells exposed to dihydroartemisinin
- vitro+vivo, ESCC, Eca109
tumCV↓, Our results proved that DHA significantly reduced the viability of Eca109 cells in a dose- and time-dependent manner.
TumCCA↑, DHA evidently induced cell cycle arrest at the G2/M phase in Eca109 cells
ROS↑, Mechanistically, DHA induced intracellular ROS generation and autophagy in Eca109 cells
TumAuto↑,
eff↓, blocking ROS by an antioxidant NAC obviously inhibited autophagy
TRF2↓, we found that telomere shelterin component TRF2 was down-regulated in Eca109 cells exposed to DHA through autophagy-dependent degradation
TumCP↓, DHA inhibits the proliferation ability of Eca109 cells in vitro and in vivo

5136- ART/DHA,    Dihydroartemisinin targets VEGFR2 via the NF-κB pathway in endothelial cells to inhibit angiogenesis
- in-vitro, Var, NA
angioG↓, The anti-malarial agent dihydroartemisinin (DHA) has strong anti-angiogenic activity.
TumCP↓, DHA shows a dose-dependent inhibition of proliferation and migration of in HUVECs.
TumCMig↓,
NF-kB↓, Our data suggested that DHA inhibits angiogenesis largely through repression of the NF-κB pathway.

3667- ART/DHA,    Artemisinin improves neurocognitive deficits associated with sepsis by activating the AMPK axis in microglia
- Review, Sepsis, NA
*cognitive↑, artemisinin administration significantly improved LPS-induced cognitive impairments assessed in Morris water maze and Y maze tests
*neuroP↑, attenuated neuronal damage and microglial activation in the hippocampus.
*TNF-α↓, artemisinin (40 μΜ) significantly reduced the production of proinflammatory cytokines (i.e., TNF-α, IL-6)
*IL6↓,
*NF-kB↓, artemisinin significantly suppressed the nuclear translocation of NF-κB and the expression of proinflammatory cytokines by activating the AMPKα1 pathway;
*AMPK↑,
*ROS↓, artemisinin protects neuronal HT-22 cells from oxidative injury by activating the Akt pathway
*Akt↑,
*MCP1↓, artemisinin reversed the LPS-induced increases in the chemokines MCP-1 and MIP-2
*MIP2↓,
*TGF-β↑, Artemisinin also significantly increased the mRNA and protein expression of TGF-β
*Inflam↓, The AMPKα1 pathway is involved in the anti-inflammatory effect of artemisinin

5134- ART/DHA,    Dihydroartemisinin induces autophagy by suppressing NF-κB activation
- in-vitro, Var, NA
TumAuto↑, Dihydroartemisinin induces autophagy by suppressing NF-κB activation
NF-kB↓,
ChemoSen↑, DHA promotes autophagy in cancer cells and provide evidence for the DHA-induced sensitization effect of some chemotherapeutics

5133- ART/DHA,    Dihydroartemisinin Exerts Anti-Tumor Activity by Inducing Mitochondrion and Endoplasmic Reticulum Apoptosis and Autophagic Cell Death in Human Glioblastoma Cells
- in-vitro, GBM, U87MG - in-vitro, GBM, U251
AntiTum↑, (DHA) has been shown to exhibit anti-tumor activity in various cancer cells.
tumCV↓, Our results proved that DHA treatment significantly reduced cell viability in a dose- and time-dependent manner by CCK-8 assay.
Apoptosis↓, DHA induced apoptosis of GBM cells through mitochondrial membrane depolarization, release of cytochrome c and activation of caspases-9.
MMP↓,
Cyt‑c↑,
Casp9↑,
CHOP↑, Enhanced expression of GRP78, CHOP and eIF2α and activation of caspase 12 were additionally confirmed that endoplasmic reticulum (ER) stress pathway of apoptosis
GRP78/BiP↑,
eIF2α↑,
Casp12↑,
ER Stress↑, DHA Induced Apoptosis through Mitochondria and Endoplasmic Reticulum (ER) Stress Pathways of Apoptosis in Human GBM Cells
TumAuto↑, ER stress and mitochondrial dysfunction were involved in the DHA-induced autophagy.
ROS↑, Further study revealed that accumulation of reactive oxygen species (ROS) was attributed to the DHA induction of apoptosis and autophagy.

5132- ART/DHA,    Dihydroartemisinin Exerts Its Anticancer Activity through Depleting Cellular Iron via Transferrin Receptor-1
- in-vitro, Liver, HepG2 - in-vitro, BC, MCF-7
Iron↓, In the current study, we found that dihydroartemisinin caused cellular iron depletion in time- and concentration-dependent manners.
TfR1/CD71↓, Moreover, dihydroartemisinin reduced the level of transferrin receptor-1 associated with cell membrane.
ROS↑, which may be a new action mechanism of DHA independently of oxidative damage.

5131- ART/DHA,    Dihydroartemisinin (DHA) induces caspase-3-dependent apoptosis in human lung adenocarcinoma ASTC-a-1 cells
- in-vitro, NSCLC, ASTC-a-1
Apoptosis↑, DHA induced apoptotic cell death in a dose- and time-dependent manner, which was accompanied by mitochondrial morphology changes, the loss of ΔΨm and the activation of caspase-3
MMP↓, DHA-induced loss of mitochondrial membrane potential (ΔΨm)
Casp3↑,
TumCP↓, proliferation of the cells could be effectively inhibited by DHA, even at a very low treating-dose (1 μg/ml) and a very short treating-time (12 h).

5130- ART/DHA,    Dihydroartemisinin Induces Apoptosis in Human Bladder Cancer Cell Lines Through Reactive Oxygen Species, Mitochondrial Membrane Potential, and Cytochrome C Pathway
- in-vitro, Bladder, T24/HTB-9
tumCV↓, DHA significantly reduced cell viability in a dose-dependent manner.
eff↓, Cytotoxicity of DHA was suppressed by N-acetylcysteine (NAC)
Apoptosis↑, induction of cell apoptosis, which were manifested by annexin V-FITC staining, activation of caspase-3
Casp3↑,
ROS↑, DHA also increased ROS generation, cytochrome c release, and loss of mitochondrial transmembrane potential (ΔΨm) in cells.
Cyt‑c↑,
MMP↓,
Bcl-2↓, downregulation of regulatory protein Bcl-2 and upregulation of Bax protein by DHA were also observed
BAX↑,
MOMP↑, Dihydroartemisinin increases mitochondrial permeability of EJ-138 and HTB-9 cells by Collapse of ΔΨm
TumCG↓, It has shown that DHA selectively inhibits the growth of many cancer cells types, such as leukemia,[29] pancreas,[30] breast[31] and prostate[32] cancers

5129- ART/DHA,    Evidence for the Involvement of Carbon-centered Radicals in the Induction of Apoptotic Cell Death by Artemisinin Compounds
- in-vitro, AML, HL-60
Casp↑, In HL-60 cells the endoperoxides induce caspase-dependent apoptotic cell death characterized by concentration- and time-dependent mitochondrial membrane depolarization, activation of caspases-3 and -7, sub-G0/G1 DNA formation
Apoptosis↑,
MMP↓,
TumCCA↑,
eff↑, have led the World Health Organization to recommend the use of ART-based combination therapies to all countries experiencing resistance to conventional monotherapies.
eff↑, The most sensitive cell lines are characterized by their rapid proliferation, often accompanied by a high intracellular iron concentration to sustain continued proliferation

4993- ART/DHA,    Dihydroartemisinin inhibits galectin-1–induced ferroptosis resistance and peritoneal metastasis of gastric cancer via the Nrf2–HO-1 pathway
- vitro+vivo, GC, NA
Ferroptosis↑, DHA suppresses galectin-1-promoted GCPM via the PI3K/Akt/Nrf2/HO-1 pathway in vitro
NRF2↓, DHA promotes ferroptosis by downregulating Nrf2/HO-1
HO-1↓,
PI3K↓, We found that DHA significantly affected galectin-1 expression and inhibited PI3K/Akt activation
Akt↓,
TumMeta↓, DHA inhibits peritoneal metastasis through the PI3K/Akt/Nrf2/HO-1 pathway in vivo

4992- ART/DHA,    Dihydroartemisinin Increases the Sensitivity of Acute Myeloid Leukemia Cells to Cytarabine via the Nrf2/HO-1 Anti-Oxidant Signaling Pathway
- in-vitro, AML, HL-60
Apoptosis↑, The combination of Ara-C and DHA synergistically promoted the apoptosis and differentiation of HL-60 cells
Diff↑,
ROS↓, Mechanistically, synergistic cytotoxic effects of Ara-C/DHA on HL-60 cells may be mediated by decreasing intracellular ROS levels
HO-1↓, However, DHA only caused the down-regulation of HO-1, whereas the expression level of nuclear Nrf2 was unaffected.
NRF2∅,

4991- ART/DHA,  doxoR,    Dihydroartemisinin alleviates doxorubicin-induced cardiotoxicity and ferroptosis by activating Nrf2 and regulating autophagy
- in-vivo, Nor, H9c2
*cardioP↑, In vivo, DHA markedly relieved Dox-induced cardiac dysfunction, attenuated oxidative stress, alleviated cardiomyocyte ferroptosis, activated Nrf2, promoted autophagy, and improved the function of lysosomes.
*ROS↓,
*Ferroptosis↓,
*NRF2↑,
Keap1↓, DHA significantly alleviates Dox-induced ferroptosis through the clearance of autophagosomes, including the selective degradation of keap1 and the recovery of lysosomes.

2578- ART/DHA,  RES,    Synergic effects of artemisinin and resveratrol in cancer cells
- in-vitro, Liver, HepG2 - in-vitro, Cerv, HeLa
Dose↝, The combination of ART and Res exhibited the strongest anticancer effect at the ratio of 1:2 (ART to Res).
TumCMig↓, combination of the two drugs also markedly reduced the ability of cell migration
Apoptosis↑, Apoptosis analysis showed that combination of ART and Res significantly increased the apoptosis and necrosis rather than use singly
necrosis↑,
ROS↑, ROS levels were elevated by combining ART with Res.
eff↑, the data suggested that the IC50 of the combination of ART and Res is lower than that of each drug used alone.

567- ART/DHA,    An Untargeted Proteomics and Systems-based Mechanistic Investigation of Artesunate in Human Bronchial Epithelial Cells
- in-vitro, Lung, BEAS-2B
NRF2↑, artesunate is Nrf2 regulator
AP-1↑,
NFAT↑,

976- ART/DHA,    Artemisinin selectively decreases functional levels of estrogen receptor-alpha and ablates estrogen-induced proliferation in human breast cancer cells
- in-vitro, BC, MCF-7
ERα/ESR1↓, downregulated ERα protein and transcripts without altering expression or activity of ERβ

957- ART/DHA,    Artemisinin inhibits the development of esophageal cancer by targeting HIF-1α to reduce glycolysis levels
- in-vitro, ESCC, KYSE150 - in-vitro, ESCC, KYSE170
TumCP↓,
TumMeta↓,
Glycolysis↓,
N-cadherin↓,
PKM2↓,
Hif1a↓,


Showing Research Papers: 1 to 50 of 94
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* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 94

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Fenton↑, 2,   Ferroptosis↑, 12,   GPx4↓, 4,   GPx4↑, 1,   GSH↓, 6,   GSH↝, 1,   HO-1↓, 2,   Iron↓, 1,   Iron↑, 6,   Keap1↓, 1,   lipid-P↑, 6,   MDA↑, 1,   Mets↑, 1,   NRF2↓, 1,   NRF2↑, 4,   NRF2∅, 1,   ROS↓, 1,   ROS↑, 20,   ROS∅, 1,  

Metal & Cofactor Biology ⓘ

Ferritin↓, 4,   NCOA4↑, 1,   NCOA4↝, 1,   Tf↓, 1,   Tf↑, 1,   TfR1/CD71↓, 1,  

Mitochondria & Bioenergetics ⓘ

ADP:ATP↑, 1,   CDC25↓, 1,   MMP↓, 4,   Raf↓, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 2,   cMyc↓, 2,   FAO↑, 1,   GlucoseCon↓, 1,   Glycolysis↓, 2,   lactateProd↓, 1,   NADPH↓, 1,   PKM2↓, 2,   PPARγ↑, 1,   SCD1↓, 1,   SIRT1↑, 1,  

Cell Death ⓘ

Akt↓, 3,   Apoptosis↓, 1,   Apoptosis↑, 9,   BAX↑, 4,   Bcl-2↓, 2,   Bcl-2↑, 1,   Casp↑, 1,   Casp12↑, 1,   Casp3↓, 1,   Casp3↑, 3,   cl‑Casp3↑, 1,   Casp8↑, 1,   Casp9↑, 3,   Cyt‑c↑, 4,   DR5↑, 1,   FADD↑, 1,   Fas↑, 1,   Ferroptosis↑, 12,   JNK↓, 1,   JNK↑, 1,   Mcl-1↓, 1,   MDM2↓, 1,   MOMP↑, 2,   necrosis↑, 1,   p27↑, 1,   p38↑, 1,   survivin↓, 2,   YAP/TEAD↓, 1,  

Transcription & Epigenetics ⓘ

other?, 1,   other↓, 2,   other↝, 1,   tumCV↓, 3,  

Protein Folding & ER Stress ⓘ

CHOP↑, 2,   eIF2α↑, 2,   ER Stress↓, 1,   ER Stress↑, 5,   GRP78/BiP↑, 5,   HSP70/HSPA5↓, 1,   HSP70/HSPA5↑, 1,   PERK↑, 2,   UPR↑, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 1,   LC3II↑, 2,   p62↓, 1,   TumAuto↑, 8,  

DNA Damage & Repair ⓘ

DNAdam↑, 4,   p16↑, 1,   P53↑, 1,   cl‑PARP↑, 1,   PCNA↓, 1,  

Cell Cycle & Senescence ⓘ

CDK1↑, 1,   CDK2↓, 2,   CDK2↑, 1,   CDK4↓, 3,   CDK4↑, 1,   CycB/CCNB1↓, 1,   cycD1/CCND1↓, 2,   cycE/CCNE↓, 2,   E2Fs↓, 1,   P21↑, 1,   TumCCA↑, 8,  

Proliferation, Differentiation & Cell State ⓘ

CD133↓, 1,   CD44↓, 1,   CSCs↓, 1,   CSCs↑, 1,   Diff↑, 2,   EMT↓, 2,   ERK↓, 1,   HH↓, 1,   IGF-1R↓, 1,   mTOR↓, 1,   mTOR↑, 1,   mTORC1↓, 1,   Nanog↓, 1,   OCT4↓, 1,   PI3K↓, 2,   STAT3↓, 2,   p‑STAT3↓, 1,   TOP2↓, 1,   TRF2↓, 1,   TumCG↓, 4,   Wnt↓, 1,  

Migration ⓘ

AP-1↓, 1,   AP-1↑, 1,   AXL↓, 1,   Ca+2↑, 2,   CAFs/TAFs↓, 1,   Cdc42↑, 1,   E-cadherin↑, 2,   Ki-67↓, 1,   MMP2↓, 2,   MMP7↓, 1,   MMP9↓, 4,   N-cadherin↓, 2,   NFAT↑, 1,   PKCδ↓, 1,   Slug↓, 1,   Snail?, 1,   TGF-β↓, 1,   TIMP2↑, 1,   TumCI↓, 1,   TumCMig↓, 3,   TumCP↓, 7,   TumCP↑, 1,   TumMeta↓, 4,   Twist↓, 1,   uPA↓, 3,   Vim↓, 1,   Zeb1↓, 1,   ZEB2↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 7,   ATF4↑, 3,   EPR↑, 1,   Hif1a↓, 2,   VEGF↓, 3,   VEGFR2↓, 1,  

Barriers & Transport ⓘ

GLUT1↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 4,   IL1β↓, 1,   IL4↓, 1,   IL8↓, 2,   M2 MC↓, 1,   NF-kB↓, 4,  

Hormonal & Nuclear Receptors ⓘ

CDK6↓, 1,   CDK6↑, 1,   CYP24A1↓, 1,   ERα/ESR1↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 2,   BioAv↑, 1,   BioAv↝, 1,   ChemoSen↑, 6,   Dose↝, 3,   eff↓, 7,   eff↑, 22,   eff↝, 2,   Half-Life?, 1,   Half-Life↓, 2,   RadioS↑, 1,   selectivity↑, 4,  

Clinical Biomarkers ⓘ

ERα/ESR1↓, 1,   Ferritin↓, 4,   Ki-67↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 5,   AntiTum↑, 1,   toxicity↓, 1,   toxicity↑, 1,   TumVol↓, 1,  
Total Targets: 188

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   Catalase↓, 1,   Catalase↑, 1,   Ferroptosis↓, 1,   Ferroptosis↑, 1,   GSH↓, 1,   GSH∅, 1,   HO-1↑, 1,   MDA↑, 1,   NRF2↑, 2,   ROS↓, 5,   SOD↓, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,  

Cell Death ⓘ

Akt↑, 1,   Casp3↓, 1,   Casp9↓, 1,   Ferroptosis↓, 1,   Ferroptosis↑, 1,   iNOS↓, 1,   p‑p38↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

ERK↑, 1,   p‑ERK↓, 1,  

Migration ⓘ

ROCK1↓, 1,   TGF-β↑, 1,  

Angiogenesis & Vasculature ⓘ

NO↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   IL1β↓, 1,   IL6↓, 3,   Inflam↓, 6,   MCP1↓, 1,   MIP2↓, 1,   MyD88↓, 1,   NF-kB↓, 4,   NF-kB↑, 1,   TLR4↓, 2,   TNF-α↓, 2,  

Synaptic & Neurotransmission ⓘ

BDNF↑, 1,  

Protein Aggregation ⓘ

NLRP3↓, 1,  

Clinical Biomarkers ⓘ

IL6↓, 3,  

Functional Outcomes ⓘ

cardioP↑, 1,   cognitive↑, 2,   memory↑, 2,   neuroP↑, 3,  
Total Targets: 43

Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:34  Target#:%  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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