Natural Compound Melatonin Suppresses Breast Cancer Development by Regulating Circadian Rhythm

Area of Science:

• Oncology
• Chronobiology
• Molecular Biology

Background:

• Breast cancer is a significant global health concern for women.
• Existing therapies have limitations, driving the need for novel treatment strategies.
• Melatonin, a circadian regulator, shows anti-tumor potential, but its circadian mechanisms are underexplored.

Purpose of the Study:

• To investigate the anti-tumor effects and underlying circadian mechanisms of melatonin in breast cancer.
• To elucidate the role of the core clock gene BMAL1 in mediating melatonin's effects.
• To identify novel therapeutic targets and strategies for breast cancer treatment.

Main Methods:

• Assessed melatonin's effects on breast cancer cell proliferation, colony formation, and apoptosis.
• Analyzed melatonin's regulation of the core clock gene BMAL1 at RNA and protein levels.
• Investigated BMAL1's role in suppressing glucose metabolism and identified downstream targets like ALDH3A1.

Main Results:

• Melatonin significantly inhibited breast cancer cell growth and induced apoptosis.
• Melatonin upregulates BMAL1, suppressing cancer cell glucose metabolism.
• A novel "melatonin-BMAL1-ALDH3A1" axis was identified, inhibiting tumor growth in vivo with potential synergistic effects with SR8278.

Conclusions:

• The "melatonin-BMAL1-ALDH3A1" axis represents a novel therapeutic target for breast cancer.
• This pathway offers a new direction for developing precision chronotherapy-based combination treatments.
• Findings lay the groundwork for future clinical applications of melatonin in breast cancer therapy.