compI Cancer Research Results

compI, mitochondrial complex-I: Click to Expand ⟱
Source:
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⟱
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

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↓,


Showing Research Papers: 1 to 5 of 5

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 5

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

Catalase↓, 1,   compI↓, 4,   GPx↓, 1,   GSH↓, 1,   GSH/GSSG↓, 1,   OXPHOS↓, 1,   ROS↑, 2,   SOD↓, 1,   Trx↓, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↓, 2,   compIII↓, 1,   MMP↓, 1,   OCR↓, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

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

Cell Death(tgid=5) ⓘ

Apoptosis↑, 1,   Casp3↑, 1,   Casp9↑, 1,   Cyt‑c↑, 1,   MAPK↓, 1,   TumCD∅, 1,  

Protein Folding & ER Stress(tgid=8) ⓘ

HSP90↓, 1,  

DNA Damage & Repair(tgid=10) ⓘ

DNAdam↑, 1,   p53 Wildtype↓, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

CDK2↓, 1,   CDK4↓, 2,   cycD1/CCND1↓, 1,   cycE/CCNE↓, 1,  

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

CSCs↓, 1,  

Migration(tgid=13) ⓘ

TumCMig↓, 1,   TumCP↓, 3,  

Angiogenesis & Vasculature(tgid=14) ⓘ

Hif1a↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

Imm↑, 1,  

Hormonal & Nuclear Receptors(tgid=20) ⓘ

CDK6↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↑, 1,   ChemoSen↑, 1,   Dose↝, 1,   eff↑, 4,   RadioS↑, 1,   selectivity↑, 3,  

Functional Outcomes(tgid=23) ⓘ

chemoP↑, 1,   chemoPv↑, 1,   hepatoP↑, 1,   NP/CIPN↓, 1,   toxicity↓, 1,   toxicity↝, 1,  
Total Targets: 49

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

compI↓, 1,   ROS↑, 1,   ROS∅, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↓, 1,   compIII↓, 1,   ETC↓, 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: 11

Scientific Paper Hit Count for: compI, mitochondrial complex-I
2 Diclofenac
2 Metformin
1 Capsaicin
1 Deguelin
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#:1228  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

 

Home Page