Osthole suppresses the proliferation and induces apoptosis via inhibiting the PI3K/AKT signaling pathway of endometrial cancer JEC cells.

Abstract

Osthole, a natural product extracted mainly from fruits of Fructus Cnidii, possesses multiple pharmacological functions, including anti-inflammatory, anti-convulsant and anticancer effects. However, the effects of osthole in endometrial cancer (EC) is not fully understood. In the present study, EC cell lines, including JEC, KLE and Ishikawa cells and normal human cervical epithelial cells (HcerEpic) were applied to detect the anticancer effect of osthole. The present study demonstrated that osthole inhibited the proliferation of JEC, KLE and Ishikawa cells, but had no cytotoxic effect on HcerEpic. Furthermore, treatment of osthole induced JEC cell apoptosis, while osthole promoted the release of pro-apoptotic proteins, Bax and activated the cleaved caspase-3, caspase-9 and PARP. Additionally, osthole significantly increased the expression of PETN and decreased the phosphorylated form of PI3K and AKT in a concentration-dependent manner. Furthermore, osthole treatment suppressed the JEC tumor cell growth in a nude mouse xenograft model in vivo, and neither renal toxicity nor hepatotoxicity was induced by the indicated concentration. Taken together, the results of the present study suggested that osthole may be a novel and potential therapeutic agent of EC.