Human hepatocellular carcinoma: Protection by melatonin

Area of Science:

• Oncology
• Molecular Biology
• Endocrinology

Background:

• Hepatocellular carcinoma (HCC) remains a significant clinical challenge with limited effective therapies.
• Melatonin, a hormone, exhibits known anti-cancer properties across various human cancers.

Purpose of the Study:

• To review the mechanistic roles of melatonin in combating human hepatocellular carcinoma (HCC).
• To explore melatonin's impact on apoptosis, proliferation, invasion, angiogenesis, autophagy, oxidative stress, tumor immunity, and MAPK signaling in HCC.

Main Methods:

• Literature search of the PubMed database using keywords: hepatocellular carcinoma (HCC), melatonin, apoptosis, proliferation, invasion, angiogenesis, autophagy, oxidative stress, tumor immunity, and mitogen-activated protein kinase (MAPK).
• Focus on human cell line studies published in English.

Main Results:

• Melatonin overcomes apoptosis resistance in HCC by activating extrinsic and intrinsic pathways.
• It induces endoplasmic reticulum (ER)- and autophagy-mediated apoptosis.
• Melatonin inhibits cancer cell proliferation, motility, and invasiveness via transcription factor modulation.
• It alleviates immunosuppression in HCC by regulating tumor-derived exosomes.
• Both pro- and anti-oxidative effects of melatonin are crucial for HCC control.
• Melatonin's actions are largely mediated through mitogen-activated protein kinase (MAPK) family members.

Conclusions:

• Melatonin demonstrates multifaceted anti-cancer activities against HCC, including apoptosis induction, proliferation inhibition, and immune modulation.
• Melatonin holds promise as a therapeutic agent or adjunct therapy for HCC, potentially enhancing chemotherapy efficacy.
• Targeting MAPK pathways is a key mechanism for melatonin's anti-HCC effects.