Oridonin is an active
diterpenoid, which was extracted from traditional Chinese herbs and had been widely used in clinical treatment nowadays.
Oridonin phosphate is one of the derivatives of
oridonin. In the present study, we explored its anti-
tumor effect and investigated the molecular mechanism of
oridonin phosphate in
breast cancer cell lines. Firstly, cell viability was analyzed by MTT assay. The
breast cancer cells were treated with increasing concentrations of
oridonin phosphate for 24, 48 and 72 h, respectively. The results demonstrated that
oridonin phosphate inhibited the proliferation of MDA-MB-436 and MDA-MB-231 cells in a dose- and time-dependent manner. Next, cell apoptosis rate was detected in
oridonin phosphate-treated
breast cancer cells by
Annexin V-FITC/PI dual staining analysis and the data demonstrated that
oridonin phosphate induced cell apoptosis of
breast cancer cells in time- and dose-dependent manner. Moreover, apoptosis-related
proteins were detected by Western blotting analysis. The results showed that the expression level of Bax was up-regulated and the expression level of Bcl-2 was down-regulated. Meanwhile, the level of cleaved
caspase-9 was significantly increased when the cells were treated with 40 μM of
oridonin phosphate for 48 h, although the expression level of
pro-caspase-9 was not obviously changed. All of the data revealed that mitochondrial apoptosis pathway may be involved in the cell apoptosis induced by
oridonin phosphate in
breast cancer cells. Importantly, the expression levels of
autophagy-related protein beclin-1 and LC3-II were significantly higher in
oridonin phosphate-treated
breast cancer cell lines MDA-MB-436 and MDA-MB-231 for 48 h. Additionally, we further explored the relationship between apoptosis and autophagy specifically induced by
oridonin phosphate in
breast cancer cells. The result showed that inhibition of autophagy suppressed the cell apoptosis in
oridonin phosphate-treated MDA-MB-436 cells. Taken together, the compound of
oridonin phosphate simultaneously induced cell apoptosis and autophagy in
breast cancer cells. Inhibition
oridonin phosphate-induced cell autophagy suppressed the progression of cell apoptosis, which revealed that
oridonin phosphate-induced autophagy participated in up-regulation of apoptosis in human
breast cancer cells. It would provide some new clues for the
therapy of
breast cancer.