ETC Cancer Research Results

ETC, Electron Transport Chain: Click to Expand ⟱
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Type:
The electron transport chain (ETC) — the mitochondrial system that produces ATP through oxidative phosphorylation — is deeply linked to cancer biology, both in tumor promotion and suppression.
-The ETC resides in the inner mitochondrial membrane and includes Complexes I–IV and ATP synthase (Complex V).
-It transfers electrons from NADH/FADH₂ to oxygen, generating ATP and reactive oxygen species (ROS) as byproducts.
-The function of the tricarboxylic acid (TCA) cycle and the mitochondrial electron transport chain (ETC) is to transfer electrons from carbon to oxygen and release energy in the form of ATP.

The #1 theory of how pulsed Magnetic Fields affect the ETC is by the RPM

The ETC consists of:
-Complex I – NADH dehydrogenase
-Complex II – Succinate dehydrogenase
-➡ Complex III – Cytochrome bc₁ complex
-Complex IV – Cytochrome c oxidase
-ATP synthase (often called Complex V)

Complex III sits between Coenzyme Q (ubiquinol) and cytochrome c.

Complex III is a major regulated source of mitochondrial ROS, especially:
-Superoxide generation at the Qo site
-ROS used for redox signaling (HIF stabilization, signaling adaptation)
-Excess ROS contributes to DNA damage and cell death


Scientific Papers found: Click to Expand⟱
6155- CoQ10,    BPGbio Highlights Groundbreaking Data on BPM31510 for Mitochondrial Diseases at the Inaugural Mitochondrial Transplantation and Next Generation Therapeutics Conference
- Review, NA, NA
*CoQ10↑, BPGbio researchers show that BPM31510 significantly increased CoQ10 levels across multiple tissues—including the brain, kidney, muscle, and heart
*BBB↑, Notably, BPM31510 achieved targeted delivery to the cerebellum, a region of the brain whose dysfunction is associated with ataxia, a hallmark symptom of mitochondrial disorders.
*ETC↑, BPM31510, a novel formulation of CoQ10, was developed to overcome these delivery challenges, helping improve mitochondrial functioning.
eff↑, BPM31510IV is BPGbio’s lead candidate in late-stage development for aggressive solid tumors such as glioblastoma multiforme (GBM) and pancreatic cancer.

6419- MEL,    The potential influence of melatonin on mitochondrial quality control: a review
- Review, Nor, NA
*mt-ACC⇅, Melatonin regulates pyruvate or fatty acid metabolism to increase the concentration of acetyl-CoA in mitochondria. these studies indicate that melatonin increases or decreases acetyl-CoA content in mitochondria to regulate mitochondrial metabolism.
*PKM1↑, melatonin increases the activity of pyruvate kinase M1/2 (PKM) to regulate glycolysis
*PKM2↑,
*Glycolysis↝,
*PDKs↑, melatonin activates pyruvate dehydrogenase kinase 4 (PDK4) to regulate acetyl-CoA content
*FAO↑, melatonin can promote fatty acid metabolism by directly enhancing β-oxidation or increasing the transfer of fatty acid-derived acetyl-CoA into mitochondria
*ETC↑, Second, melatonin can enhance the activity of the electron-transport chain (ETC) and oxidative phosphorylation (OXPHOS) to regulate mitochondrial metabolism.
*OXPHOS↑,
*ATP↑, melatonin enhanced OXPHOS and promoted adenosine triphosphate (ATP) synthesis in rat brain and liver mitochondria
Glycolysis↓, ome studies have found that melatonin drove the switch from cytosolic glycolysis to mitochondrial OXPHOS in cancer cells
OXPHOS↑,
*Ca+2↓, melatonin can regulate the membrane potential of mitochondria and decrease excessive calcium levels to enhance ETC activity to increase ATP production
*ROS↓, Melatonin exhibits superior antioxidant ability. Melatonin, as a major scavenger of reactive oxygen species (ROS), may play a pivotal role in protecting mitochondria from ROS-induced injury
*antiOx↑, These specific characteristics make melatonin a broad-spectrum antioxidant.
*SOD2↑, melatonin can upregulate the expression of superoxide dismutase (MnSOD), glutathione peroxidase (GSH-Px) and catalase (CAT) to prevent cell stress and injury
*GPx↑,
*Catalase↑,
*MFN1↑, On the one hand, melatonin increases mitochondrial fusion-related genes such as mitofusin-1 (Mfn1), mitofusin-2 (Mfn2) and optic atrophy1 (Opa1) to promote mitochondrial fusion
*MFN2↑,
*OPA1↑,
*YAP/TEAD↑, studies have found that melatonin activated the Yap-Hippo pathway to increase Opa1-related fusion
*Hippo↑,
*SIRT1↑, melatonin alleviated cardiac dysfunction induced by diabetes by upregulating SIRT1-PGC1α to inhibit the expression of Drp1
*PGC-1α↑,
*DRP1/DNM1L↓,

5254- NCL,    The magic bullet: Niclosamide
- Review, Var, NA
Wnt↓, In particular, niclosamide inhibits multiple oncogenic pathways such as Wnt/β-catenin, Ras, Stat3, Notch, E2F-Myc, NF-κB, and mTOR and activates tumor suppressor signaling pathways such as p53, PP2A, and AMPK.
β-catenin/ZEB1↓,
RAS↓,
STAT3↓,
NOTCH↓,
E2Fs↓,
mTOR↓,
eff↑, Moreover, niclosamide potentially improves immunotherapy by modulating pathways such as PD-1/PDL-1.
PD-1↓,
PD-L1↓, primarily through PD-L1 ligand downregulation in cancer cells.
BioAv↝, The original pharmacokinetics study showed that the maximal serum concentration can reach 0.25-6.0ug/ml (0.76-18.34 µM) following administration of a single 2g dose (11).
toxicity↓, a strong safety profile and tolerability in humans.
BioAv↑, A potential solution to the aforementioned challenge is niclosamide ethanolamine (NEN), a salt form of niclosamide that also functions as a mitochondrial uncoupler with a superior safety profile and enhanced bioavailability
ETC↑, NEN activates the ETC to boost NADH oxidation, thereby leading to an increased intracellular NAD+/NADH ratio and driving the TCA cycle forward.
NADH:NAD↓,
TCA↑,
Warburg↓, leading to a reversal of the Warburg effect and the induction of cellular differentiation
Diff↑,
AMPK↑, figure 3
P53↑,
PP2A↑,
HIF-1↓,
KRAS↓,
Myc↓,
RadioS↑, leading to a reversal of the Warburg effect and the induction of cellular differentiation
ChemoSen↑, Niclosamide has shown synergistic anti-tumor effects with a broad spectrum of chemotherapy drugs.
Dose↝, In this trial, either 500mg or 1000mg niclosamide was given three times daily to patients. However, the maximal plasma concentration ranged from 35.7–82 ng/mL (0.1µM-0.25 µM), a range that failed to be consistently above the minimum effective concent
Dose↑, In contrast, the ongoing clinical trial NCT02807805 is administering 1200 mg of reformulated orally bioavailable niclosamide orally (PO) three times daily to patients, resulting in 0.21µM-0.723 plasma niclosamide concentrations exceeding the therape


Showing Research Papers: 1 to 3 of 3

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 3

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

OXPHOS↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

ETC↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

AMPK↑, 1,   Glycolysis↓, 1,   NADH:NAD↓, 1,   TCA↑, 1,   Warburg↓, 1,  

Cell Death(tgid=5) ⓘ

Myc↓, 1,  

DNA Damage & Repair(tgid=10) ⓘ

P53↑, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

E2Fs↓, 1,  

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

Diff↑, 1,   mTOR↓, 1,   NOTCH↓, 1,   RAS↓, 1,   STAT3↓, 1,   Wnt↓, 1,  

Migration(tgid=13) ⓘ

KRAS↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

HIF-1↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

PD-1↓, 1,   PD-L1↓, 1,  

Protein Aggregation(tgid=19) ⓘ

PP2A↑, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↑, 1,   BioAv↝, 1,   ChemoSen↑, 1,   Dose↑, 1,   Dose↝, 1,   eff↑, 2,   RadioS↑, 1,  

Clinical Biomarkers(tgid=22) ⓘ

KRAS↓, 1,   Myc↓, 1,   PD-L1↓, 1,  

Functional Outcomes(tgid=23) ⓘ

toxicity↓, 1,  
Total Targets: 33

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 1,   Catalase↑, 1,   CoQ10↑, 1,   GPx↑, 1,   MFN1↑, 1,   MFN2↑, 1,   OPA1↑, 1,   OXPHOS↑, 1,   ROS↓, 1,   SOD2↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↑, 1,   DRP1/DNM1L↓, 1,   ETC↑, 2,   PGC-1α↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

mt-ACC⇅, 1,   FAO↑, 1,   Glycolysis↝, 1,   PDKs↑, 1,   PKM1↑, 1,   PKM2↑, 1,   SIRT1↑, 1,  

Cell Death(tgid=5) ⓘ

Hippo↑, 1,   YAP/TEAD↑, 1,  

Migration(tgid=13) ⓘ

Ca+2↓, 1,  

Barriers & Transport(tgid=15) ⓘ

BBB↑, 1,  
Total Targets: 25

Scientific Paper Hit Count for: ETC, Electron Transport Chain
1 Coenzyme Q10
1 Melatonin
1 Niclosamide (Niclocide)
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#:1386  State#:%  Dir#:2
  wNotes=on  sortOrder:rid,rpid

 

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