Daphnoretin Arrests the Cell Cycle and Induces Apoptosis in Human Breast Cancer Cells.

Abstract

Emerging evidence has shown that daphnoretin, one of the main active ingredients of Daphne giraldii Nitsche, processes antitumor activities in several tumor cells (e.g., colon cancer, lung cancer, cervical cancer, and osteosarcoma). However, the antitumor effect and its mechanism in breast cancer are unexplored. In this study, our data indicated that daphnoretin obviously suppressed the proliferation of breast cancer MCF-7 and MDA-MB-231 cells. Further studies showed that daphnoretin remarkably increased the p21 level, decreased cyclin E and CDK2 levels, and then arrested the cell cycle at the S phase. Moreover, daphnoretin obviously lowered the BCL-2 level and raised the levels of BAX and cleaved caspase-9 and -3, leading to cell apoptosis. Furthermore, daphnoretin remarkably decreased the ratio of p-PI3K/PI3K and p-AKT/AKT in breast cancer cells. Collectively, these findings demonstrated that daphnoretin could suppress breast cancer cell proliferation through cell cycle arrest and inducing apoptosis, which is related to the PI3K/AKT pathway.