Melatonin / Ac-histone H3 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


Ac-histone H3, Acetylated Histone H3: Click to Expand ⟱
Source:
Type:
Acetylated histone H3 refers to histone H3 proteins that carry acetyl groups, typically on lysine residues, which leads to a more relaxed chromatin structure and generally correlates with active gene transcription.
– Levels of Ac-histone H3 can serve as a biomarker reflecting the balance between histone acetyltransferase (HAT) activity and HDAC activity in the cell.

• Role in Cancer:
– Altered acetylation levels may contribute to dysregulated gene expression in cancer cells.
  – Low levels of histone acetylation (including Ac-histone H3) are often associated with the silencing of tumor suppressor genes, whereas increased acetylation after treatment with HDAC inhibitors is correlated with reactivation of key regulatory pathways.
  – The acetylation state of histone H3 can be used as an indicator of treatment response, and higher acetylation levels after HDAC inhibition often correlate with favorable treatment outcomes.

• Therapeutic and Immunotherapy Implications:
– HDAC inhibitors aim to increase acetylated histone levels (including Ac-histone H3), thereby promoting a more open chromatin conformation that facilitates transcription of genes involved in differentiation, apoptosis, and immune recognition.

– Increased acetylation can enhance the expression of cancer antigens and immune modulatory molecules, potentially sensitizing tumor cells to immune-mediated attack.
  – Combination therapies that include HDAC inhibitors and immunotherapeutic agents (such as checkpoint inhibitors) are being actively investigated to enhance antitumor responses by both directly affecting cancer cell survival pathways and by modulating the tumor microenvironment.


Scientific Papers found: Click to Expand⟱
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↓,

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:


Redox & Oxidative Stress

GSH↓, 1,   ROS↑, 1,  

Core Metabolism/Glycolysis

Ac-histone H3↑, 1,  

Cell Death

Apoptosis↑, 1,   BAX↑, 1,   Bcl-2↓, 1,   Casp3↑, 1,   PUMA↑, 1,  

DNA Damage & Repair

PCNA↓, 1,  

Proliferation, Differentiation & Cell State

HDAC1↓, 1,  

Migration

TumCMig↓, 1,  

Functional Outcomes

AntiCan↑, 1,  
Total Targets: 12

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: Ac-histone H3, Acetylated Histone H3
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#:983  State#:%  Dir#:2
wNotes=0 sortOrder:rid,rpid

 

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