Melatonin / PGC-1α Cancer Research Results

MEL, Melatonin: Click to Expand ⟱
Features:
Hormone in the body made by pineal gland.
• Melatonin is a potent antioxidant. It neutralizes reactive oxygen species (ROS) and reactive nitrogen species (RNS), which are involved in DNA damage and cancer progression.
• Melatonin has been shown to modulate apoptotic pathways by influencing mitochondrial permeability, cytochrome c release, and caspase activation.
• In several cancer cell models, melatonin appears to promote apoptosis in malignant cells while sparing normal cells.

The most well-known indolamines are serotonin and melatonin, both of which play significant roles in regulating mood, sleep, and overall mental well-being.

Melatonin doses (20 mg to even 40 mg per day), often given as an adjuvant treatment for cancer.
-The plasma half-life of melatonin is generally in the range of approximately 20 to 60 minutes
-It has been suggested that administering melatonin at the appropriate phase of the circadian cycle may enhance its anti-tumor activity and reduce the side effects of chemotherapy and radiation therapy.

Bio-availability: Oral melatonin has a low and variable bio-availability (often estimated between 3% and 33%), which means that only a fraction of the ingested dose reaches the bloodstream unchanged.

For proOxidant effect might need >10uM, which might be 100mg dose (assuming 10% bio-availability) Might also be required X10 levels?
-It remains unknown whether the pro-oxidant action exists in vivo. the vast majority of evidence indicates that melatonin is a potent antioxidant in vivo even at pharmacological concentrations.

Interactions:
-Melatonin could potentially add to the blood pressure–lowering properties of antihypertensive drugs.
-Patients using insulin should be monitored for changes in blood glucose levels.
-Melatonin might interact with drugs like warfarin, aspirin, or clopidogrel.(antiplatelet)


Melatonin Cancer Relevant Pathways
Rank Pathway / Axis Cancer Cells Normal Cells Label Primary Interpretation Notes
1 Circadian signaling (MT1 / MT2 receptors) ↓ proliferative circadian disruption ↑ circadian synchronization Driver Chronobiology normalization Melatonin restores circadian control; cancer cells lose growth advantages from circadian dysregulation
2 Reactive oxygen species (ROS) ↓ ROS (baseline); context-dependent ↑ stress signaling ↓ ROS (strong buffering) Driver Antioxidant dominance with signaling effects Melatonin is a potent direct and indirect antioxidant; cancer cells may still undergo stress-mediated growth inhibition
3 Mitochondrial function ↓ metabolic flexibility; ↑ apoptosis sensitivity ↑ mitochondrial efficiency Secondary Mitochondrial stabilization vs vulnerability Melatonin improves mitochondrial function in normal cells while limiting metabolic plasticity in cancer cells
4 Estrogen signaling (ERα modulation) ↓ estrogen-driven proliferation ↔ minimal Secondary Hormone-dependent growth suppression Particularly relevant in breast and hormone-responsive cancers
5 NF-κB signaling ↓ inflammatory / survival signaling ↓ inflammatory tone Secondary Anti-inflammatory modulation NF-κB suppression contributes to reduced tumor-promoting inflammation
6 Cell cycle regulation ↓ proliferation / ↑ arrest ↔ spared Phenotypic Cytostatic growth control Growth inhibition reflects upstream circadian and hormonal effects
7 Apoptosis sensitivity ↑ sensitivity to apoptosis (chemo/RT) ↓ apoptosis Phenotypic Therapy sensitization Melatonin enhances response to chemo- and radiotherapy while protecting normal tissue


PGC-1α, Peroxisome proliferator-activated receptor gamma coactivator 1-alpha: Click to Expand ⟱
Source:
Type: transcriptional coactivator
PGC-1α (Peroxisome proliferator-activated receptor gamma coactivator 1-alpha) is a transcriptional coactivator that plays a crucial role in regulating cellular energy metabolism, including mitochondrial biogenesis and function. PGC-1α is also involved in various cellular processes, including cell growth, differentiation, and survival.

In some cancers (for example, certain melanomas, breast cancers, and prostate cancers), elevated levels of PGC-1α have been observed.
– Increased PGC-1α may enhance mitochondrial function and support the energetic and biosynthetic demands of tumor cells, especially under metabolic stress or during metastasis.
Scientific Papers found: Click to Expand⟱
6419- MEL,    The potential influence of melatonin on mitochondrial quality control: a review
- Review, Nor, NA
*mt-ACC⇅, *PKM1↑, *PKM2↑, *Glycolysis↝, *PDKs↑, *FAO↑, *ETC↑, *OXPHOS↑, *ATP↑, Glycolysis↓, OXPHOS↑, *Ca+2↓, *ROS↓, *antiOx↑, *SOD2↑, *GPx↑, *Catalase↑, *MFN1↑, *MFN2↑, *OPA1↑, *YAP/TEAD↑, *Hippo↑, *SIRT1↑, *PGC-1α↑, *DRP1/DNM1L↓,
6418- MEL,  RES,    Melatonin improves mitochondrial function by preventing mitochondrial fission in cadmium-induced rat proximal tubular cell injury via SIRT1-PGC-1α pathway activation
- in-vivo, AD, NA
*neuroP↑, *DRP1/DNM1L↓, *FIS1↓, *ROS↓, *MMP↑, *SIRT1↑, *PGC-1α↑, *eff↑,

Showing Research Papers: 1 to 2 of 2

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 2

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

OXPHOS↑, 1,  

Core Metabolism/Glycolysis ⓘ

Glycolysis↓, 1,  
Total Targets: 2

Pathway results for Effect on Normal Cells:


NA, unassigned ⓘ

DRP1/DNM1L↓, 2,   FIS1↓, 1,   MFN1↑, 1,   MFN2↑, 1,   OPA1↑, 1,  

Redox & Oxidative Stress ⓘ

antiOx↑, 1,   Catalase↑, 1,   GPx↑, 1,   OXPHOS↑, 1,   ROS↓, 2,   SOD2↑, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↑, 1,   ETC↑, 1,   MMP↑, 1,   PGC-1α↑, 2,  

Core Metabolism/Glycolysis ⓘ

mt-ACC⇅, 1,   FAO↑, 1,   Glycolysis↝, 1,   PDKs↑, 1,   PKM1↑, 1,   PKM2↑, 1,   SIRT1↑, 2,  

Cell Death ⓘ

Hippo↑, 1,   YAP/TEAD↑, 1,  

Migration ⓘ

Ca+2↓, 1,  

Drug Metabolism & Resistance ⓘ

eff↑, 1,  

Functional Outcomes ⓘ

neuroP↑, 1,  
Total Targets: 27

Scientific Paper Hit Count for: PGC-1α, Peroxisome proliferator-activated receptor gamma coactivator 1-alpha
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#:122  Target#:927  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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