The effect of RIP1K signaling pathway on the cell growth inhibition and apoptosis in human breast cancer cell lines, MCF-7 and MDA-MB-468

Activation of RIP1K by different drugs has become of considerable interest as a novel molecular approach for the induction of programmed cell death in cancer cells. Breast cancer is the most common malignancy in women, therefore new molecular targets for the induction of apoptosis can be used as an important approach. Accordingly, the present study has been designed to examine the effects of RIP1K signaling pathway on the cell growth inhibition and apoptosis in human breast cancer cell lines, MCF-7 and MDA-MB-468. To investigate the effects of RIP1K on the regulation of cell growth, activator (shikonin) and inhibitor of RIP1K (Nec-1) and also caspase-8 inhibitor (Z-VAD-FMK) were employed. Cell death modes were assessed using flow cytometry, Hoechst 33258 staining, cell cycle analysis and caspase-3/8 activity assay. In this research, shikonin has been used to increase RIP1K expression. Shikonin caused a time- and dose-dependent cell growth inhibition and apoptosis and necroptosis in these cells. The role of RIP1K in the inhibition of cell growth was evaluated using Nec-1 as specific inhibitor of RIP1K. Activation of caspase 3 and -8 were observed in MDA-MB-468 cells, however in MCF-7 cells only activation of caspase-8 was detected. In the current study, shikonin caused cell growth inhibition, apoptosis and necroptosis via RIP1K overexpression in the breast cancer cell lines, MCF-7 and MDa-MB-468.

کلیدواژه ها:

RIP1K ، Breast cancer cell lines ، Apoptosis ، Necroptosis