Objective : Does 7-O-Methylpunctatin, a plant-based homoisoflavonoid, suppresses migration, invasion, and adhesion OF human breast cancer cells?
Methods: The following techniques were used: bioactivity-directed isolation, chromatographic analysis, LCMS and NMR structural characterization. MDA-MB-231 cells were used to perform wound healing migration assay, migration chamber assay, Matrigel invasion assay, adhesion to fibronectin assay, cell cycle analysis, aggregation assay senescence-associated beta-galactosidase (SA-gal) activity, caspase 3/7 activity, reactive oxygen species assay and western blotting analysis.
Results: A series of new and known homoisoflavonoid analogues were isolated from an organic extract of the bulbs of Bellevalia eigii Feinbrun (Asparagaceae), as part of a search for anticancer leads from plants. Based on the anti-proliferative screening results, 7-O-methylpunctatin was further pursued for its effects on the proliferation, migration, invasion, metastasis, and tumor growth of triple negative MDA-MB-231 breast cancer cells. 7-O-Methylpunctatin at 20 M was found to inhibit proliferation, migration, and adhesion of breast cancer cells and to attenuate invasion. 7-O-Methylpunctatin inhibitory action against migration and invasion could be attributed to induction of cell aggregation, upregulation of occludin, and downregulation of uPA. However, cell adhesion was inhibited via NF-kB downregulation. Additionally, cellular senescence, autophagy, cell cycle arrest, and reactive oxygen species were induced by 7-O-methylpunctatin treatment indicating that 7-O-methylpunctatin exerts its anti-proliferative activity by G0/G1 cell cycle arrest, and caspase pathway activation. MAPK, PI3K/Akt pathways were suppressed upon treating MDA-MB-231 cells, indicating their role in 7-O-methylpunctatin inhibition of migration and invasion.
Conclusions: The results obtained in the current study identified 7-O-methylpunctatin as a potential novel lead therapeutic treatment of breast cancer metastasis that warrants further studies.
