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Melatonin is a potential oncostatic agent to inhibit HepG2 cell proliferation through multiple pathways
Omar A Ammar1, Mohamed A El-Missiry2, Azza I Othman2
1Basic Science Department, Delta University for Science and Technology, Gamasa, Egypt.
Heliyon
|February 10, 2022
Summary
Melatonin effectively inhibits liver cancer cell proliferation and angiogenesis while inducing apoptosis and oxidative stress. These findings highlight melatonin
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Hepatocellular carcinoma (HCC) treatment relies on chemotherapy.
- Melatonin, a pineal hormone, exhibits anticancer properties, but its mechanisms require further elucidation.
- Understanding melatonin's molecular pathways is crucial for its therapeutic application in liver cancer.
Purpose of the Study:
- To investigate the molecular mechanisms underlying melatonin's antitumor effects on HepG2 liver cancer cells.
- To assess melatonin's impact on cell proliferation, cell cycle, apoptosis, and angiogenesis in HCC.
- To evaluate melatonin's influence on oxidative stress markers in HepG2 cells.
Main Methods:
- HepG2 cells were treated with melatonin (5.4 mmol/L) or left untreated (control).
- Immunohistochemistry was used to assess proliferating cell nuclear antigen (PCNA) and Ki-67 expression.
- Flow cytometry analyzed cell cycle and apoptosis, while RT-qPCR detected apoptotic markers.
- Colorimetric assays measured antioxidant and oxidative stress biomarkers.
Main Results:
- Melatonin significantly reduced HepG2 cell viability and suppressed proliferation in the G2/M phase.
- Melatonin induced apoptosis by up-regulating p53 and p21, confirmed by reduced PCNA and Ki-67.
- Melatonin repressed angiogenesis by down-regulating angiopoietin-2, VEGFR-2, and CD133.
- Melatonin increased oxidative stress, evidenced by elevated 4-hydroxynonenal and reduced glutathione and SOD activity.
Conclusions:
- Melatonin demonstrates oncostatic effectiveness against liver cancer cells (HepG2).
- Melatonin inhibits proliferation and angiogenesis, while promoting apoptosis and oxidative stress.
- These findings support melatonin's potential as a therapeutic agent for hepatocellular carcinoma.
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