OBJECTIVE: Current study was carried out to investigate the mode of cell death and role of autophagy induced by [Cu(phen)(L-tyr)Cl].3H20 in MCF-7 and MDA-MB-231 breast cancer cells.

METHODS: Growth inhibition of [Cu(phen)(L-tyr)Cl].3H20 towards MDA-MB-231 and human non-cancerous MCF10A breast cells was determined by MTT assay. Annexin-V-FITC/PI and cell cycle analysis were evaluated by flow cytometry. The expression of p53, Bax, caspase-9, caspase-7, caspase-3 and LC3 were determined using western blot analysis. The cells were then co-treated with hydroxychloroquine to ascertain the role of autophagy induced by [Cu(phen)(L-tyr)Cl].3H20.

RESULTS: [Cu(phen)(L-tyr)Cl].3H20 inhibited the growth of cancer cells dose-dependently with less toxicity towards MCF10A cells. Additionally, [Cu(phen)(L-tyr)Cl].3H20 induced apoptosis and cell cycle arrest towards MCF-7 and MDA-MB-231 breast cancer cells possibly via regulation of p53, Bax, caspase-9, caspase-3 and capase-7. The expression of LC3II was upregulated in both cancer cell lines upon treatment with [Cu(phen)(L-tyr) Cl].3H20, indicating the induction of autophagy. Co-treatment with autophagy inhibitor hydroxychloroquine significantly enhanced growth inhibition of both cell lines, suggesting that the autophagy induced by [Cu(phen)(L-tyr) Cl].3H20 in both breast cancer cells was promoting cell survival.