Abstract
Doxorubicin (DOX), a derivative of anthracyclines, is a widely used anticancer drug in the treatment of a broad spectrum of cancers. Dox is non‐selective cytotoxic drug with significant side effects on immune cells. We investigated the influence of diosgenin, a precursor of steroid hormones, on apoptosis in mouse peritoneal macrophages. Pretreatment of cells for 1 h with diosgenin (1–5 μg/ml) inhibited DX‐induced cell death in a concentration‐ and time‐dependent manner. Western blot assay showed that diosgenin suppressed caspase‐3 activation and PARP cleavage in doxorubicin‐treated macrophages, suggesting the prevention of doxorubicin‐induced apoptosis. We also found that diosgenin inhibited the down‐regulation of Bcl‐2, whereas the level of Bax and p53 expression was decreased by diosgenin treatment in Dox‐treated macrophages. Diosgenin inhibited Dox‐induced ATF‐3 expression and phosphorylation of p38 and ERK1/2. Furthermore, inhibition of ATF‐3 activity by shRNA suppressed DOX‐induced caspase‐3 activation and apoptosis. These data indicate that protective effect of diosgenin may occur through the regulation of p38, ERK1/2 and ATF‐3 signaling pathways.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call