Glaucocalyxin B induces apoptosis and autophagy in human cervical cancer cells

Abstract

Glaucocalyxin (Gln), an ent-kaurane diterpenoid isolated from the Chinese traditional medicine, Rabdosia japonica, represents a novel class of anticancer drugs. GlnA is one of the three major forms of Gln and has demonstrated potent anticancer effects in a variety of cancer types. GlnB has only one structural difference from GlnA, an acetylated hydroxyl group at C14. This acetyl group results in high liposolubility and may enhance the antitumor activity of ent-kaurane diterpenoid GlnB. However, few studies have reported the role of GlnB in cancer. The present study investigated the effect of GlnB in cervical cancer proliferation and cell death. Treatment with GlnB inhibits the proliferation of HeLa and SiHa cervical cancer cell lines in a dose-dependent manner, as assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide assays. In addition, GlnB increases the apoptotic cell population of HeLa and SiHa cells, as determined by fluorescence-activated cell sorting analysis and enhanced poly (ADP-ribose) polymerase 1 cleavage by western blotting. GlnB also induces increased light chain 3 II/I protein cleavage in both cells, indicating the induction of autophagy. Furthermore, GlnB treatment increased the expression of phosphatase and tensin homolog and decreased the expression of phosphorylated-protein kinase B (Akt) in HeLa and SiHa cells, as assessed by western blotting. Taken together, the present results demonstrated that GlnB inhibited the proliferation of human cervical cancer cells in vitro through the induction of apoptosis and autophagy, which may be mediated by the phosphatidylinositol-4,5-bisphosphate 3-kinase/Akt signaling pathway.