Inula viscosa INDUCES THE p53-DEPENDENT CELL DEATH PATHWAY IN BREAST CANCER CELLS

Abstract

Failure to activate cell death mechanisms in response to drug therapy used for breast cancer may lead to drug resistance. Therefore, knowledge of cell death mechanisms is essential for drug therapy and strategies targeting drug resistance. Although Inula viscosa (IV), widely used as a medicinal plant for traditional therapeutic purposes, can induce apoptosis in many cancers cell lines, its molecular mechanisms are not fully understood. Here, a report was presented on the apoptotic mechanism of IV in breast cancer cells. To this end, cytotoxicity of IV in breast cancer cell lines was assigned by crystal violet staining assay. RT-PCR, Western blot analysis, Annexin V-FITC apoptosis detection, p53RE luciferase assay, and p73 siRNA technique were used to evaluate the apoptotic mechanism of IV. The results indicated that N showed dose-dependent cytotoxic effects in breast cancer cell lines and induced apoptosis. As a result of IV treatment, Apaf1, Bax, Caspase 8 and 9, p53, and p73 mRNA expressions were up-regulated, but Bcl-2 gene expression level was down-regulated. In addition, it was observed that IV increased the p53 luciferase activity. Fewer cells underwent apoptosis after p73 siRNA transfection. In conclusion, IV may play a role in p53-dependent caspase activation in breast cancer cells and may also induce apoptosis in p53-mutated breast cancer cells by partially targeting p73.