ROS Cancer Research Results

ROS, Reactive Oxygen Species: Click to Expand ⟱
Source: HalifaxProj (inhibit)
Type:
Reactive oxygen species (ROS) are highly reactive molecules that contain oxygen and can lead to oxidative stress in cells. They play a dual role in cancer biology, acting as both promoters and suppressors of cancer.
ROS can cause oxidative damage to DNA, leading to mutations that may contribute to cancer initiation and progression. So normally you want to inhibit ROS to prevent cell mutations.
However excessive ROS can induce apoptosis (programmed cell death) in cancer cells, potentially limiting tumor growth. Chemotherapy typically raises ROS.
-mitochondria is the main source of reactive oxygen species (ROS) (and the ETC is heavily related)

"Reactive oxygen species (ROS) are two electron reduction products of oxygen, including superoxide anion, hydrogen peroxide, hydroxyl radical, lipid peroxides, protein peroxides and peroxides formed in nucleic acids 1. They are maintained in a dynamic balance by a series of reduction-oxidation (redox) reactions in biological systems and act as signaling molecules to drive cellular regulatory pathways."
"During different stages of cancer formation, abnormal ROS levels play paradoxical roles in cell growth and death 8. A physiological concentration of ROS that maintained in equilibrium is necessary for normal cell survival. Ectopic ROS accumulation promotes cell proliferation and consequently induces malignant transformation of normal cells by initiating pathological conversion of physiological signaling networks. Excessive ROS levels lead to cell death by damaging cellular components, including proteins, lipid bilayers, and chromosomes. Therefore, both scavenging abnormally elevated ROS to prevent early neoplasia and facilitating ROS production to specifically kill cancer cells are promising anticancer therapeutic strategies, in spite of their contradictoriness and complexity."
"ROS are the collection of derivatives of molecular oxygen that occur in biology, which can be categorized into two types, free radicals and non-radical species. The non-radical species are hydrogen peroxide (H 2O 2 ), organic hydroperoxides (ROOH), singlet molecular oxygen ( 1 O 2 ), electronically excited carbonyl, ozone (O3 ), hypochlorous acid (HOCl, and hypobromous acid HOBr). Free radical species are super-oxide anion radical (O 2•−), hydroxyl radical (•OH), peroxyl radical (ROO•) and alkoxyl radical (RO•) [130]. Any imbalance of ROS can lead to adverse effects. H2 O 2 and O 2 •− are the main redox signalling agents. The cellular concentration of H2 O 2 is about 10−8 M, which is almost a thousand times more than that of O2 •−".
"Radicals are molecules with an odd number of electrons in the outer shell [393,394]. A pair of radicals can be formed by breaking a chemical bond or electron transfer between two molecules."

Recent investigations have documented that polyphenols with good antioxidant activity may exhibit pro-oxidant activity in the presence of copper ions, which can induce apoptosis in various cancer cell lines but not in normal cells. "We have shown that such cell growth inhibition by polyphenols in cancer cells is reversed by copper-specific sequestering agent neocuproine to a significant extent whereas iron and zinc chelators are relatively ineffective, thus confirming the role of endogenous copper in the cytotoxic action of polyphenols against cancer cells. Therefore, this mechanism of mobilization of endogenous copper." > Ions could be one of the important mechanisms for the cytotoxic action of plant polyphenols against cancer cells and is possibly a common mechanism for all plant polyphenols. In fact, similar results obtained with four different polyphenolic compounds in this study, namely apigenin, luteolin, EGCG, and resveratrol, strengthen this idea.
Interestingly, the normal breast epithelial MCF10A cells have earlier been shown to possess no detectable copper as opposed to breast cancer cells [24], which may explain their resistance to polyphenols apigenin- and luteolin-induced growth inhibition as observed here (Fig. 1). We have earlier proposed [25] that this preferential cytotoxicity of plant polyphenols toward cancer cells is explained by the observation made several years earlier, which showed that copper levels in cancer cells are significantly elevated in various malignancies. Thus, because of higher intracellular copper levels in cancer cells, it may be predicted that the cytotoxic concentrations of polyphenols required would be lower in these cells as compared to normal cells."

Majority of ROS are produced as a by-product of oxidative phosphorylation, high levels of ROS are detected in almost all cancers.
-It is well established that during ER stress, cytosolic calcium released from the ER is taken up by the mitochondrion to stimulate ROS overgeneration and the release of cytochrome c, both of which lead to apoptosis.

Note: Products that may raise ROS can be found using this database, by:
Filtering on the target of ROS, and selecting the Effect Direction of ↑

Targets to raise ROS (to kill cancer cells):
• NADPH oxidases (NOX): NOX enzymes are involved in the production of ROS.
    -Targeting NOX enzymes can increase ROS levels and induce cancer cell death.
    -eNOX2 inhibition leads to a high NADH/NAD⁺ ratio which can lead to increased ROS
• Mitochondrial complex I: Inhibiting can increase ROS production
• P53: Activating p53 can increase ROS levels(by inducing the expression of pro-oxidant genes)
• Nrf2 inhibition: regulates the expression of antioxidant genes. Inhibiting Nrf2 can increase ROS levels
• Glutathione (GSH): an antioxidant. Depleting GSH can increase ROS levels
• Catalase: Catalase converts H2O2 into H2O+O. Inhibiting catalase can increase ROS levels
• SOD1: converts superoxide into hydrogen peroxide. Inhibiting SOD1 can increase ROS levels
• PI3K/AKT pathway: regulates cell survival and metabolism. Inhibiting can increase ROS levels
• HIF-1α inhibition: regulates genes involved in metabolism and angiogenesis. Inhibiting HIF-1α can increase ROS
• Glycolysis: Inhibiting glycolysis can increase ROS levels • Fatty acid oxidation: Cancer cells often rely on fatty acid oxidation for energy production.
-Inhibiting fatty acid oxidation can increase ROS levels
• ER stress: Endoplasmic reticulum (ER) stress can increase ROS levels
• Autophagy: process by which cells recycle damaged organelles and proteins.
-Inhibiting autophagy can increase ROS levels and induce cancer cell death.
• KEAP1/Nrf2 pathway: regulates the expression of antioxidant genes.
    -Inhibiting KEAP1 or activating Nrf2 can increase ROS levels and induce cancer cell death.
• DJ-1: regulates the expression of antioxidant genes. Inhibiting DJ-1 can increase ROS levels
• PARK2: regulates the expression of antioxidant genes. Inhibiting PARK2 can increase ROS levels
• SIRT1 inhibition:regulates the expression of antioxidant genes. Inhibiting SIRT1 can increase ROS levels
• AMPK activation: regulates energy metabolism and can increase ROS levels when activated.
• mTOR inhibition: regulates cell growth and metabolism. Inhibiting mTOR can increase ROS levels
• HSP90 inhibition: regulates protein folding and can increase ROS levels when inhibited.
• Proteasome: degrades damaged proteins. Inhibiting the proteasome can increase ROS levels
• Lipid peroxidation: a process by which lipids are oxidized, leading to the production of ROS.
    -Increasing lipid peroxidation can increase ROS levels
• Ferroptosis: form of cell death that is regulated by iron and lipid peroxidation.
    -Increasing ferroptosis can increase ROS levels
• Mitochondrial permeability transition pore (mPTP): regulates mitochondrial permeability.
    -Opening the mPTP can increase ROS levels
• BCL-2 family proteins: regulate apoptosis and can increase ROS levels when inhibited.
• Caspase-independent cell death: a form of cell death that is regulated by ROS.
    -Increasing caspase-independent cell death can increase ROS levels
• DNA damage response: regulates the repair of DNA damage. Increasing DNA damage can increase ROS
• Epigenetic regulation: process by which gene expression is regulated.
    -Increasing epigenetic regulation can increase ROS levels

-PKM2, but not PKM1, can be inhibited by direct oxidation of cysteine 358 as an adaptive response to increased intracellular reactive oxygen species (ROS)

ProOxidant Strategy:(inhibit the Mevalonate Pathway (likely will also inhibit GPx)
-HydroxyCitrate (HCA) found as supplement online and typically used in a dose of about 1.5g/day or more
-Atorvastatin typically 40-80mg/day, -Dipyridamole typically 200mg 2x/day Combined effect research
-Lycopene typically 100mg/day range (note debatable as it mainly lowers NRF2)

Dual Role of Reactive Oxygen Species and their Application in Cancer Therapy 
ROS-Inducing Interventions in Cancer — Canonical + Mechanistic Reference
-generated from AI and Cancer database
ROS rating:  +++ strong | ++ moderate | + weak | ± mixed | 0 none
NRF2:        ↓ suppressed | ↑ activated | ± mixed | 0 none
Conditions:  [D] dose  [Fe] metal  [M] metabolic  [O₂] oxygen
             [L] light [F] formulation [T] tumor-type [C] combination




Item ROS↑ NRF2 Condition Mechanism Class Remarks 



ROS">Piperlongumine
+++ ↓ [D][T] ROS-dominant






ROS">Shikonin
+++↓/±[D][T]ROS-dominant






ROS">Vitamin K3 (menadione)
+++↓[D]ROS-dominant






ROS">Copper (ionic / nano)
+++↓[Fe][F]ROS-dominant






ROS">Sodium Selenite
+++↓[D]ROS-dominant






ROS">Juglone
+++↓[D]ROS-dominant






ROS">Auranofin
+++↓[D]ROS-dominant






ROS">Photodynamic Therapy (PDT)
+++0[L][O₂]ROS-dominant






ROS">Radiotherapy / Radiation
+++0[O₂]ROS-dominant






ROS">Doxorubicin
+++↓[D]ROS-dominant






ROS">Cisplatin
++↓[D][T]ROS-dominant






ROS">Salinomycin
++↓[D][T]ROS-dominant






ROS">Artemisinin / DHA
++↓[Fe][T]ROS-dominant






ROS">Sulfasalazine
++↓[C][T]ROS-dominant






ROS">FMD / fasting
++↓[M][C][O₂]ROS-dominant






ROS">Vitamin C (pharmacologic)
++↓[Fe][D]ROS-dominant






ROS">Silver nanoparticles
++±[F][D]ROS-dominant






ROS">Gambogic acid
++↓[D][T]ROS-dominant






ROS">Parthenolide
++↓[D][T]ROS-dominant






ROS">Plumbagin
++↓[D]ROS-dominant






ROS">Allicin
++↓[D]ROS-dominant






ROS">Ashwagandha (Withaferin A)
++↓[D][T]ROS-dominant






ROS">Berberine
++↓[D][M]ROS-dominant






ROS">PEITC
++↓[D][C]ROS-dominant






ROS">Methionine restriction
+↓[M][C][T]ROS-secondary






ROS">DCA
+±[M][T]ROS-secondary






ROS">Capsaicin
+±[D][T]ROS-secondary






ROS">Galloflavin
+0[D]ROS-secondary






ROS">Piperine
+±[D][F]ROS-secondary






ROS">Propyl gallate
+↓[D]ROS-secondary






ROS">Scoulerine
+?[D][T]ROS-secondary






ROS">Thymoquinone
±±[D][T]Dual redox






ROS">Emodin
±±[D][T]Dual redox






ROS">Alpha-lipoic acid (ALA)
±↑[D][M]NRF2-dominant






ROS">Curcumin
±↑/↓[D][F]NRF2-dominant






ROS">EGCG
±↑/↓[D][O₂]NRF2-dominant






ROS">Quercetin
±↑/↓[D][Fe]NRF2-dominant






ROS">Resveratrol
±↑[D][M]NRF2-dominant






ROS">Sulforaphane
±↑↑[D]NRF2-dominant






ROS">Lycopene
0↑—Antioxidant






ROS">Rosmarinic acid
0↑—Antioxidant






ROS">Citrate
00—Neutral


Scientific Papers found: Click to Expand⟱
5177- BBR,    Berberine induces apoptosis in human HSC-3 oral cancer cells via simultaneous activation of the death receptor-mediated and mitochondrial pathway
- in-vitro, Oral, HMC3
TumCCA↑, Apoptosis↑, TumCG↓, Casp3↑, TumCCA↑, ROS↑, Ca+2↑, MMP↓, ER Stress↑, Cyt‑c↑,
1473- BCA,  SFN,    An Insight on Synergistic Anti-cancer Efficacy of Biochanin A and Sulforaphane Combination Against Breast Cancer
- in-vitro, BC, MCF-7
eff↑, ROS↑, other↑, ERK↓, Apoptosis↑,
5631- BCA,    Perspectives Regarding the Role of Biochanin A in Humans
- Review, Var, NA - Review, AD, NA
*BioAv↓, *Inflam↓, AntiCan↑, *neuroP↑, chemoPv↑, Dose↝, *SOD↑, *MDA↓, *BAX↓, *HSP70/HSPA5↑, *AntiDiabetic↑, *Insulin↑, *TNF-α↓, *IL1β↓, *IL6↓, *iNOS↓, *COX2↓, *MMP9↓, *ROS↓, *PGE2↓, *BACE↓, *BioAv↑, P-gp⇅,
5633- BCA,    Mechanisms Behind the Pharmacological Application of Biochanin-A: A review
- Review, Var, NA - Review, AD, NA
*AntiDiabetic↑, *neuroP↑, *toxicity↓, *CYP19↓, p‑Akt↓, mTOR↓, TumCCA↑, P21↑, Casp3↑, Bcl-2↑, Apoptosis↑, E-cadherin↓, TumMeta↓, eff↑, GSK‐3β↓, β-catenin/ZEB1↓, RadioS↑, ROS↑, Casp1↑, MMP2↓, MMP9↓, EGFR↓, ChemoSen↑, PI3K↓, MMPs↓, Hif1a↓, VEGF↓, *ROS↓, *Obesity↓, *cardioP↑, *NRF2↑, *NF-kB↓, *Inflam↓, *lipid-P↓, *hepatoP↑, *AST↓, *ALP↓, *Bacteria↓, *neuroP↑, *SOD↑, *GPx↑, *AChE↓, *BACE↓, *memory↑, *BioAv↓,
5634- BCA,    Molecular Mechanisms of Biochanin A in AML Cells: Apoptosis Induction and Pathway-Specific Regulation in U937 and THP-1
- in-vitro, AML, U937 - in-vitro, AML, THP1
Apoptosis↑, Casp7↑, PARP1↑, Bcl-2↓, Myc↓, CHOP↑, P21↑, p62↑, TumCCA↑, TXNIP↑, ROS↑, *antiOx↑, *Inflam↓, *neuroP↑, AntiCan↑, TumCP↓, angioG↓, TumMeta↓, VEGF↓, MMPs↓, tumCV↓, DNAdam↑, CHOP↑, cMyc↓, BioAv↓, Half-Life↓, BioAv↑,
5638- BCA,    Investigating the Anticancer Potential of Biochanin A in KB Oral Cancer Cells Through the NFκB Pathway
- in-vitro, Oral, NA
tumCV↓, ROS↑, MMP↓, TumCMig↓, TAC↓, lipid-P↓, NF-kB↓, Apoptosis↑,
5639- BCA,    Biochanin A Induces Apoptosis in MCF-7 Breast Cancer Cells through Mitochondrial Pathway and Pi3K/AKT Inhibition
- in-vitro, BC, NA
TumCP↓, ROS↑, Apoptosis↑, Bcl-2↓, p‑PI3K↓, p‑Akt↓, BAX↑, Casp3↑, Casp9↑, Cyt‑c↑, CycD3↓, CycB/CCNB1↓, CDK1↓, CDK2↓, CDK4↓, P21↑, p27↑, P53↑, tumCV↓, PI3K↓, Akt↓,
5582- BetA,    Targeting mitochondrial apoptosis by betulinic acid in human cancers
- Review, Var, NA
Apoptosis↑, MMP↓, Cyt‑c↑, ROS↑, NF-kB↑, angioG↓, mtDam↑, TOP1↓, selectivity↑, ChemoSen↑, TumCG↓, chemoPv↑, RadioS↑,
5591- BetA,    Advances and challenges in betulinic acid therapeutics and delivery systems for breast cancer prevention and treatment
- Review, BC, NA
BioAv↓, BioAv↑, selectivity↑, eff↑, angioG↓, *antiOx↑, *Inflam↓, MMP↓, Bcl-2↓, BAX↑, Casp9↑, Casp3↑, GRP78/BiP?, ER Stress↑, PERK↑, CHOP↑, ChemoSen↑, SESN2↑, ROS↑, MOMP↓, MAPK↑, Cyt‑c↑, AIF↑, STAT3↓, FAK↓, TIMP2↑, TumCMig↓, TumCI↓, Sp1/3/4↓, TumCCA↑, DNAdam↑,
5583- BetA,    Selective cytotoxicity of betulinic acid on tumor cell lines, but not on normal cells
- vitro+vivo, NA, NA
ROS↑, Bcl-2↓, BAX↑, TOP1↝, eff↝, toxicity↓, toxicity↓, selectivity↑,
4273- BetA,    Betulinic acid, a natural PDE inhibitor restores hippocampal cAMP/cGMP and BDNF, improve cerebral blood flow and recover memory deficits in permanent BCCAO induced vascular dementia in rats
- in-vivo, NA, NA
*neuroP↑, *BDNF↑, *ROS↓, *Inflam↓, *cognitive↑,
2722- BetA,    Betulinic Acid for Cancer Treatment and Prevention
- Review, Var, NA
MMP↓, Cyt‑c↑, cl‑Casp3↑, cl‑Casp8↑, ROS↑, NF-kB↑, TOP1↓,
2723- BetA,    Betulinic acid and oleanolic acid modulate CD81 expression and induce apoptosis in triple-negative breast cancer cells through ROS generation
- in-vitro, BC, MDA-MB-231
Apoptosis↑, tumCV↓, ROS↑,
2718- BetA,    The anti-cancer effect of betulinic acid in u937 human leukemia cells is mediated through ROS-dependent cell cycle arrest and apoptosis
- in-vitro, AML, U937
TumCCA↑, Apoptosis↑, i-ROS↑, cycA1/CCNA1↓, CycB/CCNB1↓, P21↑, Cyt‑c↑, MMP↓, Bax:Bcl2↑, Casp9↑, Casp3↑, PARP↓, eff↓, *antiOx↑, *Inflam↓, *hepatoP↑, selectivity↑, NF-kB↓, *ROS↓,
2721- BetA,    Proteomic Investigation into Betulinic Acid-Induced Apoptosis of Human Cervical Cancer HeLa Cells
- in-vitro, Cerv, HeLa
ROS↑, Dose↝, Bcl-2↓, BAX↑, ER Stress↑,
2720- BetA,    Betulinic acid induces apoptosis of HeLa cells via ROS-dependent ER stress and autophagy in vitro and in vivo
- in-vitro, Cerv, HeLa
Keap1↝, ROS↑, Ca+2↑, Beclin-1↓, GRP78/BiP↑, LC3II↑, p62↑, ERStress↑, TumAuto↑,
2719- BetA,    Betulinic Acid Restricts Human Bladder Cancer Cell Proliferation In Vitro by Inducing Caspase-Dependent Cell Death and Cell Cycle Arrest, and Decreasing Metastatic Potential
- in-vitro, CRC, T24/HTB-9 - in-vitro, Bladder, UMUC3 - in-vitro, Bladder, 5637
TumCD↑, Apoptosis↑, TumCCA↑, CycB/CCNB1↓, cycA1/CCNA1↓, CDK2↓, CDC25↓, mtDam↑, BAX↑, cl‑PARP↑, Casp3↑, Casp8↑, Casp9↑, Snail↓, Slug↓, MMP9↓, selectivity↑, MMP↓, ROS∅, TumCMig↓, TumCI↓,
2734- BetA,    Betulinic Acid Modulates the Expression of HSPA and Activates Apoptosis in Two Cell Lines of Human Colorectal Cancer
- in-vitro, CRC, HCT116 - in-vitro, CRC, SW480
tumCV↓, HSP70/HSPA5⇅, ROS↑, cl‑Casp3↑, mt-Apoptosis↑, Dose↝,
2724- BetA,    Down-regulation of NOX4 by betulinic acid protects against cerebral ischemia-reperfusion in mice
- in-vivo, Nor, NA - in-vivo, Stroke, NA
AntiTum↑, *Inflam↓, *ROS↓, *NOX4↓, *Apoptosis↓, neuroP↑,
2725- BetA,    Betulinic acid protects against renal damage by attenuation of oxidative stress and inflammation via Nrf2 signaling pathway in T-2 toxin-induced mice
- in-vivo, Nor, NA
*RenoP↑, *SOD?, *Catalase↑, *GSH↑, *ROS↓, *MDA↓, *IL1β↓, *TNF-α↓, *IL10↓, *IL6↑, *NRF2↑,
2726- BetA,    Betulinic acid induces DNA damage and apoptosis in SiHa cells
- in-vitro, Cerv, SiHa
tumCV↓, DNAdam↑, MMP↓, ROS↑, TumCCA↑, TOP1↓,
2727- BetA,    Betulinic acid in the treatment of breast cancer: Application and mechanism progress
- Review, BC, NA
mt-ROS↑, Sp1/3/4↓, TumMeta↓, GlucoseCon↓, NF-kB↓, ChemoSen↑, chemoP↑, m-Apoptosis↑, TOP1↓,
2729- BetA,    Betulinic acid in the treatment of tumour diseases: Application and research progress
- Review, Var, NA
ChemoSen↑, mt-ROS↑, STAT3↓, NF-kB↓, selectivity↑, *toxicity↓, eff↑, GRP78/BiP↑, MMP2↓, P90RSK↓, TumCI↓, EMT↓, MALAT1↓, Glycolysis↓, AMPK↑, Sp1/3/4↓, Hif1a↓, angioG↓, NF-kB↑, NF-kB↓, MMP↓, Cyt‑c↑, Casp9↑, Casp3↑, RadioS↑, PERK↑, CHOP↑, *toxicity↓,
2730- BetA,    Betulinic acid induces autophagy-dependent apoptosis via Bmi-1/ROS/AMPK-mTOR-ULK1 axis in human bladder cancer cells
- in-vitro, Bladder, T24/HTB-9
tumCV↓, TumCP↓, TumCMig↓, Casp↑, TumAuto↑, LC3B-II↑, p‑AMPK↑, mTOR↓, BMI1↓, ROS↑, eff↓,
2731- BetA,    Betulinic Acid for Glioblastoma Treatment: Reality, Challenges and Perspectives
- Review, GBM, NA - Review, Park, NA - Review, AD, NA
BBB↑, *GSH↑, *Catalase↑, *motorD↑, *neuroP↑, *cognitive↑, *ROS↓, *antiOx↑, *Inflam↓, MMP↓, STAT3↓, NF-kB↓, Sp1/3/4↓, TOP1↓, EMT↓, Hif1a↓, VEGF↓, ChemoSen↑, RadioS↑, BioAv↓,
2717- BetA,    Betulinic Acid Induces ROS-Dependent Apoptosis and S-Phase Arrest by Inhibiting the NF-κB Pathway in Human Multiple Myeloma
- in-vitro, Melanoma, U266 - in-vivo, Melanoma, NA - in-vitro, Melanoma, RPMI-8226
Apoptosis↑, TumCCA↑, MMP↓, ROS↑, eff↓, NF-kB↓, Cyt‑c↑, Casp3↑, Casp8↑, Casp9↑, cl‑PARP1↑, MDA↑, SOD↓, SOD2↓, GCLM↓, GSTA1↓, FTH1↓, GSTs↓, TumVol↓,
2716- BetA,    Cellular and molecular mechanisms underlying the potential of betulinic acid in cancer prevention and treatment
- Review, Var, NA
AntiCan↑, TumCD↑, TumCCA↑, ROS↑, NF-kB↓, Bcl-2↓, Half-Life↝, GLUT1↓, VEGF↓, PDK1↓,
2733- BetA,    Betulinic Acid Inhibits Cell Proliferation in Human Oral Squamous Cell Carcinoma via Modulating ROS-Regulated p53 Signaling
- in-vitro, Oral, KB - in-vivo, NA, NA
TumCP↓, TumVol↓, mt-Apoptosis↑, Casp3↑, Casp9↑, BAX↑, Bcl-2↑, OCR↓, TumCCA↑, ROS↑, eff↓, P53↑, STAT3↓, cycD1/CCND1↑,
2735- BetA,    Betulinic acid as apoptosis activator: Molecular mechanisms, mathematical modeling and chemical modifications
- Review, Var, NA
mt-Apoptosis↑, Casp↑, p38↑, MAPK↓, JNK↓, VEGF↓, AIF↑, Cyt‑c↑, ROS↑, Ca+2↑, ATP↓, NF-kB↓, ATF3↓, TOP1↓, VEGF↓, survivin↓, Sp1/3/4↓, MMP↓, ChemoSen↑, selectivity↑, BioAv↓, BioAv↑, BioAv↑, BioAv↑, BioAv↑,
2736- BetA,  Chemo,    Multifunctional Roles of Betulinic Acid in Cancer Chemoprevention: Spotlight on JAK/STAT, VEGF, EGF/EGFR, TRAIL/TRAIL-R, AKT/mTOR and Non-Coding RNAs in the Inhibition of Carcinogenesis and Metastasis
- Review, Var, NA
chemoPv↑, p‑STAT3↓, JAK1↓, JAK2↓, VEGF↓, EGFR↓, Cyt‑c↑, Diablo↑, AMPK↑, mTOR↓, Sp1/3/4↓, DNAdam↑, Gli1↓, GLI2↓, PTCH1↓, MMP2↓, MMP9↓, miR-21↓, SOD2↓, ROS↑, Apoptosis↑,
2738- BetA,    Betulinic Acid Suppresses Breast Cancer Metastasis by Targeting GRP78-Mediated Glycolysis and ER Stress Apoptotic Pathway
- in-vitro, BC, MDA-MB-231 - in-vitro, BC, BT549 - in-vivo, NA, NA
TumCI↓, TumCMig↓, Glycolysis↓, lactateProd↓, GRP78/BiP↑, ER Stress↑, PERK↑, p‑eIF2α↑, β-catenin/ZEB1↓, cMyc↓, ROS↑, angioG↓, Sp1/3/4↓, DNAdam↑, TOP1↓, TumMeta↓, MMP2↓, MMP9↓, N-cadherin↓, Vim↓, E-cadherin↑, EMT↓, LDHA↓, p‑PDK1↓, PDK1↓, ECAR↓, OCR↓, Hif1a↓, STAT3↓,
2758- BetA,    Betulinic Acid Attenuates Oxidative Stress in the Thymus Induced by Acute Exposure to T-2 Toxin via Regulation of the MAPK/Nrf2 Signaling Pathway
- in-vivo, Nor, NA
*ROS↓, *MDA↓, *SOD↑, *GSH↑, *p‑p38↓, *p‑JNK↓, *p‑ERK↓, *NRF2↑, *HO-1↑, *MAPK↓, *heparanase↑, *antiOx↑,
2759- BetA,    Chemopreventive and Chemotherapeutic Potential of Betulin and Betulinic Acid: Mechanistic Insights From In Vitro, In Vivo and Clinical Studies
- Review, Var, NA
chemoPv↑, ChemoSen↑, *Inflam↓, *NRF2↑, *NF-kB↓, *COX2↓, ROS↑, MMP↓, Sp1/3/4↓, VEGF↓,
2760- BetA,    A Review on Preparation of Betulinic Acid and Its Biological Activities
- Review, Var, NA - Review, Stroke, NA
AntiTum↑, Cyt‑c↑, Smad1↑, Sepsis↓, NF-kB↓, ICAM-1↓, MCP1↓, MMP9↓, COX2↓, PGE2↓, ERK↓, p‑Akt↓, *ROS↓, *LDH↓, *hepatoP↑, *SOD↑, *Catalase↑, *GSH↑, *AST↓, *ALAT↓, *RenoP↑, *ROS↓, *α-SMA↓,
2737- BetA,    Multiple molecular targets in breast cancer therapy by betulinic acid
- Review, Var, NA
TumCP↓, Cyc↓, TOP1↓, TumCCA↑, angioG↓, NF-kB↓, Sp1/3/4↓, VEGF↓, MMPs↓, ChemoSen↑, eff↑, MMP↓, ROS↑, Bcl-2↓, Bcl-xL↓, Mcl-1↓, lipid-P↑, RadioS↑, eff↑,
2739- BetA,    Glycolytic Switch in Response to Betulinic Acid in Non-Cancer Cells
- in-vitro, Nor, HUVECs - in-vitro, Nor, MEF
*Glycolysis↑, *GlucoseCon↑, *Apoptosis↓, *UCP1↓, *AMPK↑, GLUT1↑, mt-ROS↑,
2743- BetA,    Betulinic acid and the pharmacological effects of tumor suppression
- Review, Var, NA
ROS↑, MMP↓, Cyt‑c↑, Apoptosis↑, TumCCA↑, Sp1/3/4↓, STAT3↓, NF-kB↓, EMT↓, TOP1↓, MAPK↑, p38↑, JNK↑, Casp↑, Bcl-2↓, BAX↑, VEGF↓, LAMs↓,
2744- BetA,    Betulin and betulinic acid: triterpenoids derivatives with a powerful biological potential
- Review, Var, NA
Apoptosis↓, TumCCA↑, Casp9↑, Casp3↑, Casp7↑, cl‑PARP↑, MMP↓, ROS↑, TOP1↓, NF-kB↓,
2745- BetA,    Betulinic acid inhibits colon cancer cell and tumor growth and induces proteasome-dependent and -independent downregulation of specificity proteins (Sp) transcription factors
- in-vitro, CRC, RKO - in-vitro, CRC, SW480 - in-vivo, NA, NA
Apoptosis↑, TumCG↓, Sp1/3/4↓, survivin↓, VEGF↓, p65↓, EGFR↓, cycD1/CCND1↓, ROS↑, MMP↓,
2746- BetA,    Betulinic acid induces apoptosis and inhibits metastasis of human colorectal cancer cells in vitro and in vivo
- in-vitro, CRC, HCT116 - in-vivo, CRC, NA
TumCG↓, BAX↑, Bcl-2↓, ROS↑, MMP↓, TIMP2↑, TumVol↓,
2747- BetA,    Betulinic acid, a natural compound with potent anticancer effects
- Review, Var, NA
selectivity↑, Cyt‑c↑, *toxicity↓, TOP1↓, NF-kB↓, ROS↑, RadioS↑, ChemoSen↑,
2752- BetA,    Betulinic acid: a natural product with anticancer activity
- Review, Var, NA
selectivity↑, ChemoSen↑, RadioS↑, MMP↓, cl‑Casp3↑, Cyt‑c↑, ROS↑, NF-kB↑, TOP1↓,
2753- BetA,    Betulinic acid induces apoptosis by regulating PI3K/Akt signaling and mitochondrial pathways in human cervical cancer cells
- in-vitro, Cerv, HeLa
PI3K↓, p‑Akt↓, ROS↑, TumCCA↑, p27↑, P21↑, mt-Apoptosis↑, BAD↑, Casp9↑, MMP↓, eff↓,
2756- BetA,    Betulinic acid inhibits growth of hepatoma cells through activating the NCOA4-mediated ferritinophagy pathway
- in-vitro, HCC, HUH7 - in-vitro, HCC, H1299
TumCP↓, ROS↑, antiOx↓, TumCG↓, TumCMig↓, NRF2↓, GPx4↓, HO-1↓, NCOA4↑, FTH1↓, Ferritin↑, Ferroptosis↑, GSH↓, MDA↓,
1566- betaCar,  Lyco,    Antioxidant and pro-oxidant effects of lycopene in comparison with beta-carotene on oxidant-induced damage in Hs68 cells
- in-vitro, Nor, HS68
*ROS↑, *ROS⇅, *Dose?,
5561- betaCar,    Carotenoid Supplementation for Alleviating the Symptoms of Alzheimer’s Disease
- Review, AD, NA
*ROS↓, *cognitive↑, *BBB↑, *lipid-P↓, *eff↑,
5726- BF,    Bufalin exerts antitumor effects in neuroblastoma via the induction of reactive oxygen species-mediated apoptosis by targeting the electron transport chain
- Review, neuroblastoma, SK-N-BE
Apoptosis↑, TumCP↓, TumCMig↓, MMP↓, ROS↑, ETC↓, Bcl-2↓, BAX↑, cl‑Casp3↑, cl‑PARP↑, eff↓, TumCG↓, Ki-67↓, PCNA↓,
5727- BF,    Bufalin Inhibits Proliferation and Induces Apoptosis in Osteosarcoma Cells by Downregulating MicroRNA-221
- in-vitro, OS, U2OS
TumCP↓, Apoptosis↑, ROS↑, miR-221↓,
5686- BJ,  BRU,    A review of Brucea javanica: metabolites, pharmacology and clinical application
- Review, Var, NA
AntiTum↑, other↝, ChemoSen↑, QoL↑, chemoP↑, *Inflam↓, NF-kB↓, TumCP↓, TumCI↓, TumMeta↓, Hif1a↓, NRF2↓, STAT3↓, COX2↓, Casp3↑, Casp9↑, ROS↑, EGFR↓, NRF2↑,
5689- BJ,    Brucea javanica oil inhibited the proliferation, migration, and invasion of oral squamous carcinoma by regulated the MTFR2 pathway
- vitro+vivo, Oral, CAL27
TumCP↓, TumCMig↓, TumCI↓, SOD2↓, H2O2↓, OXPHOS↑, Glycolysis↓, ROS↑, RadioS↑, Hif1a↓, TumCG↓,

Showing Research Papers: 451 to 500 of 2169
Prev Page 10 of 44 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 2169

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↓, 1,   ATF3↓, 1,   Ferroptosis↑, 1,   GCLM↓, 1,   GPx4↓, 1,   GSH↓, 1,   GSTA1↓, 1,   GSTs↓, 1,   H2O2↓, 1,   HO-1↓, 1,   Keap1↝, 1,   lipid-P↓, 1,   lipid-P↑, 1,   MDA↓, 1,   MDA↑, 1,   NRF2↓, 2,   NRF2↑, 1,   OXPHOS↑, 1,   ROS↑, 36,   ROS∅, 1,   i-ROS↑, 1,   mt-ROS↑, 3,   SOD↓, 1,   SOD2↓, 3,   TAC↓, 1,  

Metal & Cofactor Biology ⓘ

Ferritin↑, 1,   FTH1↓, 2,   NCOA4↑, 1,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 2,   ATP↓, 1,   CDC25↓, 1,   ETC↓, 1,   MMP↓, 21,   mtDam↑, 2,   OCR↓, 2,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 2,   p‑AMPK↑, 1,   cMyc↓, 2,   ECAR↓, 1,   GlucoseCon↓, 1,   Glycolysis↓, 3,   lactateProd↓, 1,   LDHA↓, 1,   PDK1↓, 2,   p‑PDK1↓, 1,  

Cell Death ⓘ

Akt↓, 1,   p‑Akt↓, 4,   Apoptosis↓, 1,   Apoptosis↑, 16,   m-Apoptosis↑, 1,   mt-Apoptosis↑, 4,   BAD↑, 1,   BAX↑, 9,   Bax:Bcl2↑, 1,   Bcl-2↓, 10,   Bcl-2↑, 2,   Bcl-xL↓, 1,   Casp↑, 3,   Casp1↑, 1,   Casp3↑, 11,   cl‑Casp3↑, 4,   Casp7↑, 2,   Casp8↑, 2,   cl‑Casp8↑, 1,   Casp9↑, 10,   Cyt‑c↑, 14,   Diablo↑, 1,   Ferroptosis↑, 1,   JNK↓, 1,   JNK↑, 1,   MAPK↓, 1,   MAPK↑, 2,   Mcl-1↓, 1,   MOMP↓, 1,   Myc↓, 1,   p27↑, 2,   p38↑, 2,   survivin↓, 2,   TumCD↑, 2,  

Kinase & Signal Transduction ⓘ

Sp1/3/4↓, 11,  

Transcription & Epigenetics ⓘ

miR-21↓, 1,   other↑, 1,   other↝, 1,   tumCV↓, 7,  

Protein Folding & ER Stress ⓘ

CHOP↑, 4,   p‑eIF2α↑, 1,   ER Stress↑, 4,   ERStress↑, 1,   GRP78/BiP?, 1,   GRP78/BiP↑, 3,   HSP70/HSPA5⇅, 1,   PERK↑, 3,  

Autophagy & Lysosomes ⓘ

Beclin-1↓, 1,   LC3B-II↑, 1,   LC3II↑, 1,   p62↑, 2,   SESN2↑, 1,   TumAuto↑, 2,  

DNA Damage & Repair ⓘ

DNAdam↑, 5,   P53↑, 2,   PARP↓, 1,   cl‑PARP↑, 3,   PARP1↑, 1,   cl‑PARP1↑, 1,   PCNA↓, 1,  

Cell Cycle & Senescence ⓘ

CDK1↓, 1,   CDK2↓, 2,   CDK4↓, 1,   Cyc↓, 1,   cycA1/CCNA1↓, 2,   CycB/CCNB1↓, 3,   cycD1/CCND1↓, 1,   cycD1/CCND1↑, 1,   CycD3↓, 1,   P21↑, 5,   TumCCA↑, 15,  

Proliferation, Differentiation & Cell State ⓘ

BMI1↓, 1,   EMT↓, 4,   ERK↓, 2,   Gli1↓, 1,   GSK‐3β↓, 1,   mTOR↓, 3,   P90RSK↓, 1,   PI3K↓, 3,   p‑PI3K↓, 1,   PTCH1↓, 1,   STAT3↓, 7,   p‑STAT3↓, 1,   TOP1↓, 12,   TOP1↝, 1,   TumCG↓, 7,  

Migration ⓘ

Ca+2↑, 3,   E-cadherin↓, 1,   E-cadherin↑, 1,   FAK↓, 1,   GLI2↓, 1,   Ki-67↓, 1,   LAMs↓, 1,   MALAT1↓, 1,   miR-221↓, 1,   MMP2↓, 4,   MMP9↓, 5,   MMPs↓, 3,   N-cadherin↓, 1,   Slug↓, 1,   Smad1↑, 1,   Snail↓, 1,   TIMP2↑, 2,   TumCI↓, 6,   TumCMig↓, 8,   TumCP↓, 10,   TumMeta↓, 5,   TXNIP↑, 1,   Vim↓, 1,   β-catenin/ZEB1↓, 2,  

Angiogenesis & Vasculature ⓘ

angioG↓, 6,   EGFR↓, 4,   Hif1a↓, 6,   VEGF↓, 11,  

Barriers & Transport ⓘ

BBB↑, 1,   GLUT1↓, 1,   GLUT1↑, 1,   P-gp⇅, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   ICAM-1↓, 1,   JAK1↓, 1,   JAK2↓, 1,   MCP1↓, 1,   NF-kB↓, 15,   NF-kB↑, 4,   p65↓, 1,   PGE2↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 4,   BioAv↑, 6,   ChemoSen↑, 12,   Dose↝, 3,   eff↓, 6,   eff↑, 6,   eff↝, 1,   Half-Life↓, 1,   Half-Life↝, 1,   RadioS↑, 8,   selectivity↑, 9,  

Clinical Biomarkers ⓘ

EGFR↓, 4,   Ferritin↑, 1,   Ki-67↓, 1,   Myc↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 3,   AntiTum↑, 3,   chemoP↑, 2,   chemoPv↑, 4,   neuroP↑, 1,   QoL↑, 1,   toxicity↓, 2,   TumVol↓, 3,  

Infection & Microbiome ⓘ

Sepsis↓, 1,  
Total Targets: 196

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 5,   Catalase↑, 3,   GPx↑, 1,   GSH↑, 4,   HO-1↑, 1,   lipid-P↓, 2,   MDA↓, 3,   NOX4↓, 1,   NRF2↑, 4,   ROS↓, 11,   ROS↑, 1,   ROS⇅, 1,   SOD?, 1,   SOD↑, 4,  

Mitochondria & Bioenergetics ⓘ

Insulin↑, 1,   UCP1↓, 1,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1,   AMPK↑, 1,   GlucoseCon↑, 1,   Glycolysis↑, 1,   LDH↓, 1,  

Cell Death ⓘ

Apoptosis↓, 2,   BAX↓, 1,   iNOS↓, 1,   p‑JNK↓, 1,   MAPK↓, 1,   p‑p38↓, 1,  

Protein Folding & ER Stress ⓘ

HSP70/HSPA5↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

p‑ERK↓, 1,  

Migration ⓘ

heparanase↑, 1,   MMP9↓, 1,   α-SMA↓, 1,  

Barriers & Transport ⓘ

BBB↑, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   IL10↓, 1,   IL1β↓, 2,   IL6↓, 1,   IL6↑, 1,   Inflam↓, 10,   NF-kB↓, 2,   PGE2↓, 1,   TNF-α↓, 2,  

Synaptic & Neurotransmission ⓘ

AChE↓, 1,   BDNF↑, 1,  

Protein Aggregation ⓘ

BACE↓, 2,  

Hormonal & Nuclear Receptors ⓘ

CYP19↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 2,   BioAv↑, 1,   Dose?, 1,   eff↑, 1,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   ALP↓, 1,   AST↓, 2,   IL6↓, 1,   IL6↑, 1,   LDH↓, 1,  

Functional Outcomes ⓘ

AntiDiabetic↑, 2,   cardioP↑, 1,   cognitive↑, 3,   hepatoP↑, 3,   memory↑, 1,   motorD↑, 1,   neuroP↑, 6,   Obesity↓, 1,   RenoP↑, 2,   toxicity↓, 4,  

Infection & Microbiome ⓘ

Bacteria↓, 1,  
Total Targets: 67

Scientific Paper Hit Count for: ROS, Reactive Oxygen Species
121 Silver-NanoParticles
92 Quercetin
88 Magnetic Fields
80 Curcumin
74 Thymoquinone
55 Shikonin
54 Vitamin C (Ascorbic Acid)
52 Resveratrol
49 Berberine
49 Sulforaphane (mainly Broccoli)
47 Lycopene
44 Radiotherapy/Radiation
43 Baicalein
42 Alpha-Lipoic-Acid
40 Selenite (Sodium)
40 Ashwagandha(Withaferin A)
40 Piperlongumine
39 Selenium NanoParticles
38 Artemisinin
38 EGCG (Epigallocatechin Gallate)
37 Betulinic acid
36 Hydrogen Gas
34 Rosmarinic acid
33 Capsaicin
32 Silymarin (Milk Thistle) silibinin
29 Propolis -bee glue
29 Fisetin
28 Apigenin (mainly Parsley)
27 Honokiol
26 Allicin (mainly Garlic)
25 Chemotherapy
25 Phenethyl isothiocyanate
24 Luteolin
24 Magnetic Field Rotating
23 Copper and Cu NanoParticles
22 Vitamin K2
21 doxorubicin
21 Gambogic Acid
20 chitosan
20 Chlorogenic acid
20 Chrysin
20 Juglone
19 Cisplatin
18 Boron
17 salinomycin
17 Parthenolide
16 Urolithin
15 Coenzyme Q10
14 Photodynamic Therapy
14 Auranofin
14 Boswellia (frankincense)
14 Carnosic acid
14 Carvacrol
14 Phenylbutyrate
13 Selenium
13 Ellagic acid
13 Emodin
13 Pterostilbene
12 Caffeic acid
12 VitK3,menadione
11 5-fluorouracil
11 Astaxanthin
11 Dichloroacetate
11 Graviola
11 Piperine
10 Melatonin
10 Ursolic acid
10 diet FMD Fasting Mimicking Diet
10 Ferulic acid
10 Plumbagin
9 SonoDynamic Therapy UltraSound
9 Andrographis
9 Bacopa monnieri
9 borneol
8 Electrical Pulses
8 Sulfasalazine
8 Hyperthermia
8 Methylene blue
8 Moringa oleifera
8 Propyl gallate
7 3-bromopyruvate
7 Gold NanoParticles
7 Gemcitabine (Gemzar)
7 Metformin
7 Berbamine
7 brusatol
7 Carnosine
7 Celastrol
7 Hydroxycinnamic-acid
7 diet Methionine-Restricted Diet
7 Disulfiram
7 HydroxyTyrosol
6 2-DeoxyGlucose
6 immunotherapy
6 Biochanin A
6 Butyrate
6 Chlorophyllin
6 Citric Acid
6 Aflavin-3,3′-digallate
6 Nimbolide
5 Docetaxel
5 Brucea javanica
5 Bromelain
5 erastin
5 Thymol-Thymus vulgaris
5 Chocolate
5 Spermidine
5 Crocetin
5 Huperzine A/Huperzia serrata
5 Garcinol
5 HydroxyCitric Acid
5 Magnolol
5 nicotinamide adenine dinucleotide
5 Rutin
4 chemodynamic therapy
4 EMF
4 Zinc
4 Vitamin E
4 diet Short Term Fasting
4 γ-linolenic acid (Borage Oil)
4 Magnesium
4 Naringin
4 Taurine
3 5-Aminolevulinic acid
3 Anthocyanins
3 Glucose
3 temozolomide
3 Black phosphorus
3 Paclitaxel
3 Catechins
3 Choline
3 Cinnamon
3 Date Fruit Extract
3 Oxygen, Hyperbaric
3 Shilajit/Fulvic Acid
3 Ginkgo biloba
3 Orlistat
3 MCToil
3 Methylsulfonylmethane
3 Mushroom Lion’s Mane
3 Oleuropein
3 Shankhpushpi
3 Vitamin B1/Thiamine
2 5-Hydroxytryptophan
2 Astragalus
2 Aromatherapy
2 Ascorbyl Palmitate
2 Atorvastatin
2 Aloe anthraquinones
2 beta-glucans
2 Baicalin
2 beta-carotene(VitA)
2 Bufalin/Huachansu
2 Bruteridin(bergamot juice)
2 Caffeic Acid Phenethyl Ester (CAPE)
2 Cat’s Claw
2 Calorie Restriction Mimetics
2 Galantamine
2 Folic Acid, Vit B9
2 Fenbendazole
2 Galloflavin
2 Potassium
2 Methyl Jasmonate
2 Methylglyoxal
2 Myricetin
2 Vitamin B3,Niacin
2 Niclosamide (Niclocide)
2 Pachymic acid
2 Sanguinarine
2 Psoralidin
2 Radio Frequency
2 Sesame seeds and Oil
2 Iron
2 Salvia miltiorrhiza
2 Vitamin D3
1 cetuximab
1 Anzaroot, Astragalus fasciculifolius Bioss
1 entinostat
1 Camptothecin
1 Resiquimod
1 Ajoene (compound of Garlic)
1 Acetyl-l-carnitine
1 alpha Linolenic acid
1 Anti-oxidants
1 Sorafenib (brand name Nexavar)
1 tamoxifen
1 almonertinib
1 D-limonene
1 epirubicin
1 Lapatinib
1 Ras-selective lethal 3
1 Cannabidiol
1 Celecoxib
1 Aspirin -acetylsalicylic acid
1 Rivastigmine
1 methylseleninic acid
1 Docosahexaenoic Acid
1 diet Ketogenic
1 diet Plant based
1 Exercise
1 Fucoidan
1 Gallic acid
1 verapamil
1 hydroxychloroquine
1 Ginseng
1 hydrogen sulfide
1 Rapamycin
1 Ivermectin
1 lambertianic acid
1 Myrrh
1 N-Acetyl-Cysteine
1 Oleocanthal
1 sericin
1 benzo(a)pyrene
1 Hyperoside
1 Kaempferol
1 Perilla
1 Salvia officinalis
1 Oxaliplatin
1 Scoulerine
1 polyethylene glycol
1 acetaminophen
1 Formononetin
1 Silicic Acid
1 Squalene
1 Osimertinib
1 Adagrasib
1 Glutathione
1 statins
1 Safflower yellow
1 triptolide
1 Vitamin A, Retinoic Acid
1 Vitamin B12
1 Vitamin B2,Riboflavin
1 Vitamin B5,Pantothenic Acid
1 glucose deprivation
1 Transarterial Chemoembolization
1 probiotics
1 xanthohumol
1 Zinc Oxide
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#:%  Target#:275  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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