Zn(II) 5,5-diethylbarbiturate complex selectively induces apoptosis in breast cancer and breast cancer stem-like cells

Abstract

The biological activities of Zn(II) compounds have been extensively studied in recent years. In this study, the growth suppressive effect of Zn(II) 5,5-diethylbarbiturate complex on MCF-7 and MDA-MB-231 human breast cancer cells was determined by SRB and ATP viability assays and apoptosis-inducing effect by double staining method. Significant increase in cytokeratin 18 level, caspase 3/7 activity and annexin-V upregulation prove that Zn(II) complex has apoptotic effect in breast cancer cells. Intrinsic apoptosis pathway in MCF-7 cells and extrinsic apoptosis pathway in MDA-MB-231 cells was determined by Western blot (PARP, Cleave PARP, BAX, COX4, RIP, Caspase 8, Split Caspase 8, DR4 and B-Actin) and RT-PCR (PARP, Fas, Bcl-2, TNF10A, P53) analysis. No reduction of viability was found in MCF-710A healthy breast cells treated with Zn(II) complex. In breast cancer stem-like cells (MCF-7s), the Zn(II) complex was found to have a cytotoxic effect and to activate the apoptotic pathway. As a result, it was concluded that Zn(II) complex has anti-proliferative and apoptotic effects on breast cancer and breast cancer stem-like cells. Also this complex prevents the metastatic effect of cancer cells and does not effect to healthy cells so this complex has a specific effect on cancer cells. These findings might shed light on the discovery of new chemotherapeutic agents.