Melatonin / STAT3 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


STAT3, Signal transducer and activator of transcription 3: Click to Expand ⟱
Source:
Type: Oncogene
Stat3 (Signal Transducer and Activator of Transcription 3) is a transcription factor that plays a crucial role in various cellular processes, including cell growth, survival, differentiation, and immune response.
Stat3 is frequently found to be constitutively activated in many types of cancers, including breast, prostate, lung, and head and neck cancers. (associated with poor prognosis and reduced survival.)

-STAT3 is typically activated by cytokines (such as IL-6) and growth factors binding to their respective receptors.
-Activated STAT3 upregulates the expression of genes that promote cell cycle progression (e.g., cyclin D1) and anti-apoptotic proteins (e.g., Bcl-2, Bcl-xL).


Scientific Papers found: Click to Expand⟱
5384- AsP,  MEL,    Synergistic Anticancer Effect of Melatonin and Ascorbyl Palmitate Nanoformulation: A Promising Combination for Cancer Therapy
- in-vivo, Var, NA
AntiCan↑, TumCG↓, Apoptosis↑, DNAdam↑, TumCCA↑, IL6↓, STAT3↓, TumCP↓, Ki-67↓, TumCI↓, TumMeta↓, MMP9↓, eff↑, *Catalase↑, *SOD↑, *GSH↑, *MDA↓, *NO↓, *antiOx↑, *hepatoP↑, *RenoP↑,
1782- MEL,    Melatonin in Cancer Treatment: Current Knowledge and Future Opportunities
- Review, Var, NA
AntiCan↑, Apoptosis↑, TumCP↓, TumCG↑, TumMeta↑, ChemoSideEff↓, radioP↑, ChemoSen↑, *ROS↓, *SOD↑, *GSH↑, *GPx↑, *Catalase↑, Dose∅, VEGF↓, eff↑, Hif1a↓, GLUT1↑, GLUT3↑, CAIX↑, P21↑, p27↑, PTEN↑, Warburg↓, PI3K↓, Akt↓, NF-kB↓, cycD1/CCND1↓, CDK4↓, CycB/CCNB1↓, CDK4↓, MAPK↑, IGF-1R↓, STAT3↓, MMP9↓, MMP2↓, MMP13↓, E-cadherin↑, Vim↓, RANKL↓, JNK↑, Bcl-2↓, P53↑, Casp3↑, Casp9↑, BAX↑, DNArepair↑, COX2↓, IL6↓, IL8↓, NO↓, T-Cell↑, NK cell↑, Treg lymp↓, FOXP3↓, CD4+↑, TNF-α↑, Th1 response↑, BioAv↝, RadioS↑, OS↑,

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:


Core Metabolism/Glycolysis

CAIX↑, 1,   Warburg↓, 1,  

Cell Death

Akt↓, 1,   Apoptosis↑, 2,   BAX↑, 1,   Bcl-2↓, 1,   Casp3↑, 1,   Casp9↑, 1,   JNK↑, 1,   MAPK↑, 1,   p27↑, 1,  

DNA Damage & Repair

DNAdam↑, 1,   DNArepair↑, 1,   P53↑, 1,  

Cell Cycle & Senescence

CDK4↓, 2,   CycB/CCNB1↓, 1,   cycD1/CCND1↓, 1,   P21↑, 1,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State

IGF-1R↓, 1,   PI3K↓, 1,   PTEN↑, 1,   STAT3↓, 2,   TumCG↓, 1,   TumCG↑, 1,  

Migration

E-cadherin↑, 1,   Ki-67↓, 1,   MMP13↓, 1,   MMP2↓, 1,   MMP9↓, 2,   Treg lymp↓, 1,   TumCI↓, 1,   TumCP↓, 2,   TumMeta↓, 1,   TumMeta↑, 1,   Vim↓, 1,  

Angiogenesis & Vasculature

Hif1a↓, 1,   NO↓, 1,   VEGF↓, 1,  

Barriers & Transport

GLUT1↑, 1,   GLUT3↑, 1,  

Immune & Inflammatory Signaling

CD4+↑, 1,   COX2↓, 1,   FOXP3↓, 1,   IL6↓, 2,   IL8↓, 1,   NF-kB↓, 1,   NK cell↑, 1,   T-Cell↑, 1,   Th1 response↑, 1,   TNF-α↑, 1,  

Hormonal & Nuclear Receptors

RANKL↓, 1,  

Drug Metabolism & Resistance

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

Clinical Biomarkers

IL6↓, 2,   Ki-67↓, 1,  

Functional Outcomes

AntiCan↑, 2,   ChemoSideEff↓, 1,   OS↑, 1,   radioP↑, 1,  
Total Targets: 63

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress

antiOx↑, 1,   Catalase↑, 2,   GPx↑, 1,   GSH↑, 2,   MDA↓, 1,   ROS↓, 1,   SOD↑, 2,  

Angiogenesis & Vasculature

NO↓, 1,  

Functional Outcomes

hepatoP↑, 1,   RenoP↑, 1,  
Total Targets: 10

Scientific Paper Hit Count for: STAT3, Signal transducer and activator of transcription 3
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#:373  State#:%  Dir#:1
wNotes=0 sortOrder:rid,rpid

 

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