Molecular Mechanisms Underlying the Anti-Tumor Activity of Lotus-Derived Alkaloids in Breast Cancer

Area of Science:

• Phytochemistry
• Molecular Biology
• Oncology

Background:

• Breast cancer, especially triple-negative breast cancer (TNBC), presents significant therapeutic challenges due to molecular heterogeneity and resistance.
• Novel therapeutic strategies are urgently needed to combat aggressive breast cancer subtypes.

Purpose of the Study:

• To systematically investigate the anti-cancer potential of Nelumbo nucifera-derived alkaloids: liensinine (LIE), isoliensinine (ISO), and neferine (NEF).
• To elucidate the molecular mechanisms underlying their efficacy, particularly in TNBC models.

Main Methods:

• Treatment of multiple breast cancer cell lines, including TNBC models, with LIE, ISO, and NEF.
• Assessment of cell viability, apoptosis induction, and cell cycle progression.
• Transcriptomic profiling and molecular pathway analysis (MAPK, mTOR).

Main Results:

• LIE, ISO, and NEF demonstrated potent growth-inhibitory effects.
• Apoptosis induction and cell cycle arrest at G1 and G2/M phases were observed.
• Liensinine (LIE) was identified as a key effector, reprogramming transcription and targeting MAPK and mTOR pathways.

Conclusions:

• Nelumbo nucifera alkaloids exhibit significant anti-cancer activity against breast cancer, including TNBC.
• Liensinine's mechanism involves targeting MAPK and mTOR signaling pathways.
• These findings support the development of N. nucifera alkaloids as novel therapeutic agents for advanced breast cancer.