Berbamine Exerts Anticancer Effects on Human Colon Cancer Cells Via Induction of Autophagy and Apoptosis, Inhibition of Cell Migration and MEK/ERK Signalling Pathway.

Purpose: Berbamine is a plant-derived alkaloid with amazing and wide diversity of pharmacological properties which range from antimicrobial and anticancer. Nonetheless, the anticancer properties of Berbamine have not been thoroughly evaluated against colon cancer cells. This study was undertaken to evaluate the anticancer effects of Berbamine against the human colon cancer cell line HT-29. Methods: CCK-8 assay was used to determine the cell viability. DAPI and propidium iodide (PI) staining assays were used for the detection of apoptosis. Electron microscopy was used for the determination of autophagy. Wound healing assay was used to monitor cell migration. Protein expression was determined by western blotting. Results: The results showed that Berbamine caused a remarkable decrease in the HT-29 cell viability with an IC50 of 14 mu M, while the high IC50 of Berbamine against the normal CDD-18Co cells indicated low toxicity of this mol-ecule against the normal cells. DAPI and PI staining assays showed nuclear fragmentation, indicative of apoptosis in HT-29 cells. Berbamine also caused activation of caspase-3 and 9 and increased the Bax/Bcl-2 ratio. Electron microscopic analysis showed that Berbamine triggered the development of autophagic vesicles in the HT-29 cells which was concomitant with the increase in protein levels of LC3B-I, ATG-5, ATG-12 and Beclin-1. Wound healing assay showed that Berbamine decreased the migration potential of the HT29 and also blocked the MEK/ERK signalling pathway in colon cancer cells. Conclusion: Berbamine may prove an efficient lead molecule for the development of more potent anticancer agents through semi-synthetic approaches.