Melatonin / Bcl-2 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


Bcl-2, B-cell CLL/lymphoma 2: Click to Expand ⟱
Source: HalifaxProj (inhibit) CGL-Driver Genes
Type: Antiapoptotic Oncogene
The proteins of BCL-2 family are classified into three subgroups, i.e., the anti-apoptotic/pro-survival proteins represented by BCL-2 and BCL-XL, the pro-apoptotic proteins represented by BAX and Bak, and the pro-apoptotic BH3-only proteins represented by BAD and BID.
Since the expression of Bcl-2 protein in tumor cells is much higher than that in normal cells, inhibitors targeting it have little effect on normal cells.
Scientific Papers found: Click to Expand⟱
4818- ASTX,  MEL,    Effect of astaxanthin and melatonin on cell viability and DNA damage in human breast cancer cell lines
- in-vitro, BC, MDA-MB-231 - in-vitro, BC, T47D - in-vitro, Nor, MCF10
TumCD↑, DNAdam↑, *antiOx↑, *AntiTum↑, Inflam↓, tumCV↓, Bcl-2↓, Apoptosis↓, selectivity↑, eff↑, Dose↓,
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↑,
1063- MEL,    HDAC1 inhibition by melatonin leads to suppression of lung adenocarcinoma cells via induction of oxidative stress and activation of apoptotic pathways
- in-vitro, Lung, A549 - in-vitro, Lung, PC9
AntiCan↑, TumCMig↓, GSH↓, Casp3↑, Apoptosis↑, ROS↑, HDAC1↓, Ac-histone H3↑, PUMA↑, BAX↑, PCNA↓, Bcl-2↓,
1313- VitD3,  MEL,    The effects of melatonin and vitamin D3 on the gene expression of BCl-2 and BAX in MCF-7 breast cancer cell line
- in-vitro, BC, MCF-7
BAX↑, Bcl-2↓, Bax:Bcl2↑, eff↑,

Showing Research Papers: 1 to 4 of 4

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 4

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

GSH↓, 1,   ROS↑, 1,  

Core Metabolism/Glycolysis ⓘ

Ac-histone H3↑, 1,   CAIX↑, 1,   Warburg↓, 1,  

Cell Death ⓘ

Akt↓, 1,   Apoptosis↓, 1,   Apoptosis↑, 2,   BAX↑, 3,   Bax:Bcl2↑, 1,   Bcl-2↓, 4,   Casp3↑, 2,   Casp9↑, 1,   JNK↑, 1,   MAPK↑, 1,   p27↑, 1,   PUMA↑, 1,   TumCD↑, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   DNArepair↑, 1,   P53↑, 1,   PCNA↓, 1,  

Cell Cycle & Senescence ⓘ

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

Proliferation, Differentiation & Cell State ⓘ

HDAC1↓, 1,   IGF-1R↓, 1,   PI3K↓, 1,   PTEN↑, 1,   STAT3↓, 1,   TumCG↑, 1,  

Migration ⓘ

E-cadherin↑, 1,   MMP13↓, 1,   MMP2↓, 1,   MMP9↓, 1,   Treg lymp↓, 1,   TumCMig↓, 1,   TumCP↓, 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↓, 1,   IL8↓, 1,   Inflam↓, 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,   Dose∅, 1,   eff↑, 3,   RadioS↑, 1,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

IL6↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 2,   ChemoSideEff↓, 1,   OS↑, 1,   radioP↑, 1,  
Total Targets: 71

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

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

Functional Outcomes ⓘ

AntiTum↑, 1,  
Total Targets: 7

Scientific Paper Hit Count for: Bcl-2, B-cell CLL/lymphoma 2
4 Melatonin
1 Astaxanthin
1 Vitamin D3
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#:27  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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