Melatonin / p27/CDKN1B 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


p27/CDKN1B, p27kip1: Click to Expand ⟱
Source:
Type:
The cyclin-dependent kinase (Cdk) inhibitor p27 regulates cell proliferation, cell motility and apoptosis, and is inactivated through various means in many types of human cancer.

CDKN1B - Cyclin-Dependent Kinase Inhibitor 1B / p27

Abbreviation: CDKN1B, p27, p27Kip1

Type: Cyclin-dependent kinase inhibitor / cell-cycle regulator

Function: CDKN1B/p27 inhibits cyclin-CDK complexes, particularly cyclin E-CDK2 and cyclin A-CDK2, thereby restricting G1/S cell-cycle progression. It also regulates differentiation, transcription, cytoskeletal organization, cell migration, and cellular responses to growth-factor signaling.

Cancer: ↕ Context-dependent, but predominantly tumor-suppressive. Reduced nuclear p27 expression or functional loss can promote uncontrolled proliferation, tumor progression, and treatment resistance. However, cytoplasmic p27 can acquire CDK-independent pro-oncogenic functions that promote cell motility, invasion, and aggressive tumor behavior.
Scientific Papers found: Click to Expand⟱
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/CDKN1B↑, 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/PTGS2↓, IL6↓, IL8↓, NO↓, T-Cell↑, NK cell↑, Treg lymp↓, FOXP3↓, CD4+↑, TNF-α↑, Th1 response↑, BioAv↝, RadioS↑, OS↑,

Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:


Core Metabolism/Glycolysis(tgid=4) ⓘ

CAIX↑, 1,   Warburg↓, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 1,   Apoptosis↑, 1,   BAX↑, 1,   Bcl-2↓, 1,   Casp3↑, 1,   Casp9↑, 1,   JNK↑, 1,   MAPK↑, 1,   p27/CDKN1B↑, 1,  

DNA Damage & Repair(tgid=10) ⓘ

DNArepair↑, 1,   P53↑, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

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

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

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

Migration(tgid=13) ⓘ

E-cadherin↑, 1,   MMP13↓, 1,   MMP2↓, 1,   MMP9↓, 1,   Treg lymp↓, 1,   TumCP↓, 1,   TumMeta↑, 1,   Vim↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

Hif1a↓, 1,   NO↓, 1,   VEGF↓, 1,  

Barriers & Transport(tgid=15) ⓘ

GLUT1↑, 1,   GLUT3↑, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

CD4+↑, 1,   COX2/PTGS2↓, 1,   FOXP3↓, 1,   IL6↓, 1,   IL8↓, 1,   NF-kB↓, 1,   NK cell↑, 1,   T-Cell↑, 1,   Th1 response↑, 1,   TNF-α↑, 1,  

Hormonal & Nuclear Receptors(tgid=20) ⓘ

RANKL↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

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

Clinical Biomarkers(tgid=22) ⓘ

IL6↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 1,   ChemoSideEff↓, 1,   OS↑, 1,   radioP↑, 1,  
Total Targets: 56

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

Catalase↑, 1,   GPx↑, 1,   GSH↑, 1,   ROS↓, 1,   SOD↑, 1,  
Total Targets: 5

Scientific Paper Hit Count for: p27/CDKN1B, p27kip1
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#:468  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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