compI Cancer Research Results

compI, mitochondrial complex-I: Click to Expand ⟱
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Type:
Mitochondrial complex I (NADH:ubiquinone oxidoreductase) is the largest enzyme of the oxidative phosphorylation system. Its function is essential for bioenergetics and redox balance. Altered expression of its subunits can lead to changes in tumor metabolism, reactive oxygen species (ROS) generation, and apoptotic sensitivity—all of which may impact tumor growth and patient outcomes.

Commonly Reported Complex I Subunit:
-Increased expression of NDUFA4L2 has been associated with poor prognosis
-Reduced expression of core complex I subunits (such as NDUFS1 and NDUFS3) may correlate with a poorer overall survival in some cancers
-NDUFV1 have been linked to adverse clinical outcomes

-Dysregulation of complex I may alter ROS production. In some cancers, controlled ROS production can aid in signaling that promotes cell proliferation or survival, while excessive ROS can trigger cell death. Genes like NDUFA4L2 are also linked with hypoxia, a common feature in the tumor microenvironment.
Scientific Papers found: Click to Expand⟱
7967- BUL,    Mode of action of bullatacin: a potent antitumor and pesticidal annonaceous acetogenin
- in-vivo, Ovarian, A2780S - in-vivo, AML, L1210
compI↓, Their toxicity in both cases probably arises from their strong inhibition of mitochondrial electron transport with a specific action at complex I
ETC↓,

7974- BUL,    Selective action of acetogenin mitochondrial complex I inhibitors
- in-vitro, Colon, SW480
compI↓, Indirect evidence suggests that the insecticidal effects of ACGs are due to their inhibition of mitochondrial complex I
NADH↓, moderate correlation with their NADH-oxidase inhibition activity

7977- BUL,    Mitochondria-mediated apoptosis induced by acetogenins from Porcelia macrocarpa (Annonaceae) in K562 chronic myeloid leukemia cells
- in-vitro, AML, K562
compI↓, bullatacin, have been reported to impair mitochondrial function, including inhibition of mitochondrial respiratory chain complex I.
tumCV↓, acetogenins 1 and 3 significantly reducing leukemia cell viability
SOD2↑, Mechanistic studies revealed that acetogenin 1 increased mitochondrial superoxide production, partially dissipated mitochondrial membrane potential, disrupted calcium homeostasis,
MMP↓,
Ca+2↝,
Casp3↑, activation of caspase-9 and caspase-3, consistent with intrinsic apoptotic signaling
Casp9↑,

2014- CAP,    Role of Mitochondrial Electron Transport Chain Complexes in Capsaicin Mediated Oxidative Stress Leading to Apoptosis in Pancreatic Cancer Cells
- in-vitro, PC, Bxpc-3 - in-vitro, Nor, HPDE-6 - in-vivo, PC, AsPC-1
ROS↑, ROS was about 4–6 fold more as compared to control and as early as 1 h after capsaicin treatment in BxPC-3 and AsPC-1 cells
*ROS∅, but not in normal HPDE-6 cells
selectivity↑, only small ~1.2fold ROS increase in normal cell
compI↓, capsaicin inhibits about 2.5–9% and 5–20% of complex-I activity
compIII↓, and 8–75% of complex-III activity in BxPC-3 and AsPC-1 cells respectively
eff↑, which was attenuable by SOD, catalase and EUK-134.
selectivity↑, capsaicin treatment failed to inhibit complex-I or complex-III activities in normal HPDE-6 cells
ATP↓, ATP levels were drastically suppressed by capsaicin treatment in both BxPC-3 and AsPC-1 cells
Cyt‑c↑, release of cytochrome c and cleavage of both caspase-9 and caspase-3 due to disruption of mitochondrial membrane potential
Casp9↑,
Casp3↑,
MMP↓,
SOD↓, mice orally fed with 2.5 mg/kg capsaicin show decreased SOD activity and an increase in GSSG/GSH levels as compared to controls
GSH/GSSG↓, mice orally fed with 2.5 mg/kg capsaicin
Apoptosis↑, Capsaicin triggers apoptosis in pancreatic cancer cells but not in normal HPDE-6 cells
*toxicity∅, Capsaicin triggers apoptosis in pancreatic cancer cells but not in normal HPDE-6 cells
GSH↓, Taken together, our results suggest that depletion of GSH level and inhibition of SOD, catalase and GPx by capsaicin disturbs the cellular redox homeostasis resulting in increased oxidative stress.
Catalase↓,
GPx↓,
Dose↝, 13.2 mg dose of capsaicin for a 60 kg person

6671- Deg,    A Novel Derivative of the Natural Agent Deguelin for Cancer Chemoprevention and Therapy
- in-vitro, Nor, BEAS-2B - in-vitro, Lung, H1299 - in-vitro, Lung, H460
HSP90↓, natural compound deguelin has promising preventive and therapeutic activity against diverse cancers by directly binding to heat-shock protein 90 (Hsp90) and thus suppressing its function.
toxicity↝, Potential side effects of deguelin over a certain dose, however, could be a substantial obstacle to its clinical use.
eff↑, One derivative, SH-14, showed several features of potential superiority for clinical use:
chemoPv↑, novel derivative SH-14 has strong potential for cancer chemoprevention and therapy, with equivalent efficacy and lesser toxicity (versus deguelin).
p53 Wildtype↓, hich leads to decreased expression of a number of Hsp90 client proteins, including mutated p53, cyclin-dependent kinase 4, mitogen-activated protein kinase (MAPK) kinase-1/2 (MEK1/2), Akt and hypoxia-inducible factor (HIF)-1α,
CDK4↓,
MAPK↓,
Hif1a↓,
selectivity↑, Deguelin has antitumor activity in vitro or in vivo at doses producing no toxic effects to normal cells or tissues and so may be a promising cancer preventive and therapeutic agent
compI↓, Researchers originally identified deguelin as a potent mitochondria complex I, NADH dehydrogenase inhibitor and implicated mitochondrial dysfunction and diminished complex I activity as factors in the pathophysiology of Parkinson’s disease (PD;
TumCP↓, Synthesis of five derivatives of deguelin that inhibit Hsp90 function and lung cancer cell proliferation
BioAv↑, SH-14 has better aqueous solubility than deguelin

6699- DFC,    Mitochondrial H2O2 Is a Central Mediator of Diclofenac-Induced Hepatocellular Injury
- vitro+vivo, Nor, NA
*ROS↑, The detrimental hepatotoxicity of diclofenac, a widely used NSAID, is primarily connected to oxidative damage in mitochondria, which are the primary source of reactive oxygen species (ROS).
*hepatoP↓, diclofenac’s harmful hepatotoxicity is primarily related to the effects of ROS on mitochondria
*eff↑, PrxIII or other antioxidants targeting mitochondrial H2O2 could be explored as potential therapeutic agents to protect against the hepatotoxicity associated with NSAID use.
*ATP↓, diclofenac and metabolites impede ATP production and oxidative phosphorylation in rat liver mitochondria
OXPHOS↓,
*ETC↓, diclofenac inhibits the electron transport chain (ETC) complexes I and III, which could thereby lead to electron leakage from the respiratory chain, slowing mitochondrial respiration
*compI↓,
*compIII↓,

6696- DFC,  MET,    Combined Modulation of Tumor Metabolism by Metformin and Diclofenac in Glioma
- in-vitro, GBM, GBM
compI↓, Previous research has shown that metformin, which is an inhibitor of complex I of the respiratory chain, may inhibit some brain tumor initiating cells (BTICs), albeit at dosages that are too high for clinical use.
Glycolysis↓, explored whether a combined treatment of metformin and diclofenac, which is a non-steroidal anti-inflammatory drug (NSAID) shown to inhibit glycolysis
OCR↓, However, we observed that metformin inhibited cellular oxygen consumption and increased extracellular lactate levels, indicating glycolytic rescue mechanisms
Glycolysis↑,
lactateProd↓, Combined treatment inhibited metformin-induced lactate increase.
eff↑, Combined treatment may reduce the effective doses of the single agents and prevent metabolic rescue mechanisms.
TumCP↓, Combined Treatment of Metformin and Diclofenac Impairs Cell Proliferation and Migration
TumCMig↓,
TumCD∅, Metformin, Diclofenac, and Combined Treatment at Low Doses Do Not Increase Cell Death

7234- GBE,    Ginkgo Biloba Extract Ameliorates Oxidative Phosphorylation Performance and Rescues Aβ-Induced Failure
- in-vitro, Nor, NA
*antiOx↑, We observed a general antioxidant effect of GBE leading to an increase of the coupling state of mitochondria as well as energy homeostasis and a reduction of ROS levels in control cells and in APP cells.
*ROS↓,
*OXPHOS↑, Improvement of the OXPHOS efficiency was stronger in APP cells than in control cells.
*OCR↑, GBE improved oxygen consumption in isolated mitochondria from APP cells and led to an up-regulation of mitochondrial DNA
*compI↓, Complex I activity significantly increased after GBE treatment selectively in APP cells

7282- Gins,    Ginsenoside Rh2 stimulates the production of mitochondrial reactive oxygen species and induces apoptosis of cervical cancer cells by inhibiting mitochondrial electron transfer chain complex
- in-vitro, Cerv, NA
compI↓, G-Rh2 significantly inhibited the activity of ETC complexes I, III and V.
compIII↓,
ETC↓,
ROS↑, molecular docking, confirmed that G-Rh2 was highly likely to induce mitochondrial ROS production and promote cell apoptosis by targeting the ETC complex, especially for ETC complex III.
Apoptosis↑,
tumCV↓, G-Rh2 inhibits the viability of cervical cancer cells but is not cytotoxic to End1/e6e7 cells
selectivity↑,
MMP↓, G-Rh2 treatment significantly reduced the MMP in HeLa cells.
ATP↓, G-Rh2 treatment reduced cellular ATP levels by 10.4% (35 µM) and 49.1% (45 µM) in HeLa cells and by 7.5% (35 µM) and 35.2% (45 µM) in C33A cells
OXPHOS↓, G-Rh2 treatment of HeLa cells resulted in a rapid decline of OXPHOS.
ECAR↓, G-Rh2 reduced ECAR, which reflects glycolytic capacity.
Glycolysis↓, Glycolysis, glycolytic capacity and glycolytic reserve were all significantly inhibited by G-Rh2

8027- IVM,    Progress in Understanding the Molecular Mechanisms Underlying the Antitumour Effects of Ivermectin
- Review, Var, NA
*AntiP↑, Ivermectin was soon adopted in 1987 as a human medicine that was originally used for the treatment of onchocerciasis, a parasitic infection.
TumCD↑, Ivermectin causes cell death in cancer cell lines by inducing PAK1-mediated cytostatic autophagy,
PAK1↑,
TumAuto↑,
Casp↑, caspase-dependent apoptosis and immunogenic cell death (ICD) through the modulation of some pathways, including the WNT-T cell factor (TCF), Hippo and Akt/mTOR pathways.
ICD↑,
TCF↝, Ivermectin Serves as a WNT-T Cell Factor (TCF) Pathway Response Blocker
Hippo↓,
Akt↓, Ivermectin inhibits the Akt/mTOR signalling pathway by increasing the ubiquitination-mediated degradation of PAK1,
mTOR↓,
angioG↓, In addition, ivermectin induces the multidrug resistance protein (MDR), has potent anti-mitotic activity, targets angiogenesis and inhibits cancer stem-like cells (CSCs).
CSCs↓, Ivermectin Is an Inhibitor of CSCs
MMP↓, collapse of the mitochondrial membrane potential (ΔΨm) and the release of cytochrome c,
Cyt‑c↑,
Apoptosis↑, ivermectin induces apoptosis in glioblastoma and HeLa cells by enhancing cytochrome c release, upregulating Bax and p53 expression, downregulating Bcl-2 expression and decreasing the levels of cyclin E, cyclin D1, CDK2, CDK6 and CDK4
BAX↑,
P53↑,
Bcl-2↓,
cycE/CCNE↓,
cycD1/CCND1↓,
CDK2↓,
CDK6↓,
CDK4↓,
YAP/TEAD↓, Ivermectin Inhibits Proliferation by Inhibiting Yea-Associated Protein 1 (YAP1)
TFE3↑, Ivermectin treatment increases TFE3(Ser321) dephosphorylation, activates TFE3 nuclear translocation and stimulates activation of the TFE3 reporter in human melanoma cells
mTORC1↓, Ivermectin treatment also clearly decreases phosphorylation of the mTORC1 substrate p-70S6K, which results in induction of mTORC1 deactivation.
mitResp↓, Ivermectin Inhibits Mitochondrial Respiration
OCR↓, inhibitory effect of ivermectin on the basal oxygen consumption rate (OCR) and maximum OCR in U87, T98G
compI↓, ivermectin inhibits mitochondrial respiration by decreasing the activity of respiratory complex I enzyme
MMP↓, ivermectin decreased the mitochondrial membrane potential,
ROS↑, Consistently, obviously increased levels of ROS and mitochondrial superoxide as well as decreased ATP levels were also found in glioblastoma, HBMECs and chronic myeloid leukaemia (CML) cells treated with ivermectin
SOD2↑,
ATP↓,
eff↓, (ALCAR, a mitochondrial fuel) and N-acetyl-l-cysteine (NAC, an antioxidant) reversed the inhibitory effects of ivermectin in renal cell carcinoma (RCC) cells, which indicates that mitochondria are the target of ivermectin.
mitA↓, Ivermectin Exerts Anti-Mitotic Activity
P-gp/ABCB1↓, Ivermectin Is a P-Glycoprotein (P-Gp) Inhibitor
TumVol↓, After 10 to 42 days, treatment with ivermectin can reduced the tumour volume by more than 50%.

8047- IVM,    The multitargeted drug ivermectin: from an antiparasitic agent to a repositioned cancer drug
- Review, Var, NA
Half-Life↝, it has a mean peak plasma level of ~4 h after oral administration with a second peak at 6-12 h because of enterohepatic recycling. its half-life is approximately 19 h
MDR1↓, Ivermectin as an inhibitor of the multi-drug resistance (MDR) phenotype
P-gp/ABCB1↓, concluding that ivermectin is also a substrate and an inhibitor of P-glycoprotein
mtDam↑, Ivermectin as an inductor of mitochondrial dysfunction and oxidative damage
ROS↑,
OCR↓, ivermectin inhibits in a dose-dependent manner the basal and maximum oxygen consumption rate (OCR), most likely by decreasing the enzyme activity of respiratory complex I but not II, IV or V,
compI↓,
MMP↓, both the membrane potential and electrochemical proton gradient decrease while a significant increase in mitochondrial superoxide and decreased ATP are observed.
mt-SOD↑,
ATP↓,
p‑Akt↓, Results showed that ivermectin decreases phosphorylation of Akt (S473), mTOR (S2481)
p‑mTOR↓,
eff↓, abolition of the inhibitory effect of ivermectin in these renal cancer cell lines when co-treated with acetyl-L-carnitine (ALCAR) or N-acetyl-L-cysteine (NAC)
ICD↑, Ivermectin as an inductor of immunogenic cell death (ICD)
TumAuto↑, Ivermectin as an inductor of autophagy
PAK1↓, Ivermectin in ovarian and glioblastoma cancer cell lines promotes ubiquitination-mediated degradation of the oncogenic kinase PAK1
Wnt↓, Ivermectin as an inhibitor of the WNT-TCF pathway
TCF↓,
Nanog↓, 0.5 µM it reduces NANOG and SOX2 gene expression by 80%,
SOX2↓,
CSCs↓, Ivermectin as a stem-cell cancer inhibitor
CD44↓, ivermectin preferentially inhibits the viability of CSCs-enriched populations (CD44+/CD24-) and cells growing in spheroids,
CD24↓,
Dose↝, Thus, the in vitro and in vivo results with ivermectin strongly suggest that its antitumor effects in cancer patients can be achieved at feasible doses.

8046- IVM,    Antibiotic ivermectin selectively induces apoptosis in chronic myeloid leukemia through inducing mitochondrial dysfunction and oxidative stress
- in-vitro, CML, NA
TumCD↑, ivermectin selectively kills chronic myeloid leukemia (CML) cells via inducing mitochondrial dysfunctions and oxidative stress. I
mtDam↑,
ROS↓,
selectivity↑, Ivermectin is significantly more effective in inducing caspase-dependent apoptosis in CML cell line K562 and primary CML CD34 than normal bone marrow (NBM) CD34 cells.
compI↓, ivermectin inhibits respiratory complex I activity and suppresses mitochondrial respiration in K562 and CML CD34 cells.
mitResp↓,
eff↓, Antioxidant NAC rescues ivermectin's effects, confirming oxidative stress as the mechanism of its action in CML.

5800- MET,    Metformin as anticancer agent and adjuvant in cancer combination therapy: Current progress and future prospect
- Review, Var, NA
ChemoSen↑, Some combination therapy strategies including metformin combined with chemotherapy, radiotherapy, targeted therapy and immunotherapy have been proven to have more significant antitumor effects
RadioS↑,
Imm↑,
*AntiDiabetic↑, Metformin, the preferred glucose-lowering drug for patients with T2DM, is typically an adenosine monophosphate-activated protein kinase (AMPK) activator
*AMPK↑,
TumCP↓, AMPK restores the normal function of the liver and other tissues in diabetic patients as well as stops the metabolism of rapidly proliferating tumors
hepatoP↑,
ATP↓, . This leads to a decrease in intracellular ATP and an increase in AMP levels, which inhibits gluconeogenesis and further activates AMPK.
AMP↑,
glucoNG↓,
ROS↑, metformin can also promote reactive oxygen species (ROS) production by inhibiting mitochondrial respiratory-chain complex I, which can lead to DNA damage and gene mutation [23]
compI↓,
DNAdam↑,
CSCs↓, The advantage of metformin combined with chemotherapy is related to killing cancer stem cells [30].
NP/CIPN↓, metformin could improve the adverse effects of neuropathy (PN) in paclitaxel-treated breast cancer patients
chemoP↑, Thus, metformin may be able to be used as a chemoprotective agent, reducing the toxicity of chemotherapy and ameliorating adverse effects.
toxicity↓, The safety and tolerability of metformin were confirmed, but a large number of phase III clinical trials are still needed to follow up the study
Trx↓, Metformin radiosensitizes ductal breast cancer MCF7 cells by increasing intracellular reactive oxygen species (ROS) production through decreased thioredoxin (Trx) expression
eff↑, In addition, metformin may act in combination with the aspirin metabolite salicylic acid to enhance the proliferation inhibition of radiotherapy on prostate cancer
cycD1/CCND1↓, addition of metformin reduced the expression levels of cyclin D1, CDK4, CDK6, cyclin E, and CDK2 in gastric cancer cells
CDK4↓,
CDK6↓,
cycE/CCNE↓,
CDK2↓,

7382- MFrot,    Inhibition of mitochondrial NADH:ubiquinone oxidoreductase by spinning oscillating magnetic fields causes toxicity in cancer cells
- vitro+vivo, GBM, NA
ROS↑, (sOMF) produced by this device is reactive oxygen species-dependent persistent inhibition of mitochondrial complex I.
compI↓,
DNAdam↑, Steps downstream of this mechanism involve the production of oxidative stress, DNA damage, G1 phase cell cycle arrest, and caspase-dependent apoptosis.
TumCCA↑,
Casp↓,
Apoptosis↑,
mt-NADH↓, Inhibition of mitochondrial NADH


Showing Research Papers: 1 to 14 of 14

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 14

Pathway results for Effect on Cancer / Diseased Cells:


NA, unassigned(tgid=0) ⓘ

TFE3↑, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

Catalase↓, 1,   compI↓, 12,   GPx↓, 1,   GSH↓, 1,   GSH/GSSG↓, 1,   ICD↑, 2,   NADH↓, 1,   mt-NADH↓, 1,   OXPHOS↓, 2,   ROS↓, 1,   ROS↑, 6,   SOD↓, 1,   mt-SOD↑, 1,   SOD2↑, 2,   Trx↓, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↓, 5,   compIII↓, 2,   ETC↓, 2,   mitResp↓, 2,   MMP↓, 6,   mtDam↑, 2,   OCR↓, 3,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

AMP↑, 1,   ECAR↓, 1,   glucoNG↓, 1,   Glycolysis↓, 2,   Glycolysis↑, 1,   lactateProd↓, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 1,   p‑Akt↓, 1,   Apoptosis↑, 4,   BAX↑, 1,   Bcl-2↓, 1,   Casp↓, 1,   Casp↑, 1,   Casp3↑, 2,   Casp9↑, 2,   Cyt‑c↑, 2,   Hippo↓, 1,   MAPK↓, 1,   TumCD↑, 2,   TumCD∅, 1,   YAP/TEAD↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

tumCV↓, 2,  

Protein Folding & ER Stress(tgid=8) ⓘ

HSP90↓, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

TumAuto↑, 2,  

DNA Damage & Repair(tgid=10) ⓘ

DNAdam↑, 2,   P53↑, 1,   p53 Wildtype↓, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

CDK2↓, 2,   CDK4↓, 3,   cycD1/CCND1↓, 2,   cycE/CCNE↓, 2,   mitA↓, 1,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

CD24↓, 1,   CD44↓, 1,   CSCs↓, 3,   mTOR↓, 1,   p‑mTOR↓, 1,   mTORC1↓, 1,   Nanog↓, 1,   SOX2↓, 1,   TCF↓, 1,   TCF↝, 1,   Wnt↓, 1,  

Migration(tgid=13) ⓘ

Ca+2↝, 1,   PAK1↓, 1,   PAK1↑, 1,   TumCMig↓, 1,   TumCP↓, 3,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 1,   Hif1a↓, 1,  

Barriers & Transport(tgid=15) ⓘ

P-gp/ABCB1↓, 2,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

Imm↑, 1,  

Hormonal & Nuclear Receptors(tgid=20) ⓘ

CDK6↓, 2,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↑, 1,   ChemoSen↑, 1,   Dose↝, 2,   eff↓, 3,   eff↑, 4,   Half-Life↝, 1,   MDR1↓, 1,   RadioS↑, 1,   selectivity↑, 5,  

Functional Outcomes(tgid=23) ⓘ

chemoP↑, 1,   chemoPv↑, 1,   hepatoP↑, 1,   NP/CIPN↓, 1,   toxicity↓, 1,   toxicity↝, 1,   TumVol↓, 1,  
Total Targets: 93

Pathway results for Effect on Normal Cells:


NA, unassigned(tgid=0) ⓘ

AntiP↑, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 1,   compI↓, 2,   OXPHOS↑, 1,   ROS↓, 1,   ROS↑, 1,   ROS∅, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↓, 1,   compIII↓, 1,   ETC↓, 1,   OCR↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

AMPK↑, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

eff↑, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiDiabetic↑, 1,   hepatoP↓, 1,   toxicity∅, 1,  
Total Targets: 16

Scientific Paper Hit Count for: compI, mitochondrial complex-I
3 Bullatacin
3 Ivermectin
2 Diclofenac
2 Metformin
1 Capsaicin
1 Deguelin
1 Ginkgo biloba
1 Ginseng
1 Magnetic Field Rotating
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

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