Ponicidin induces apoptosis of human cervical cancer HeLa cell line through the PI 3 K / Akt and MAPK signaling pathways

Ponicidin, an ent-kaurane diterpenoid of Rabdosia rubescens or Isodon japonicas, has been associated with a broad range of biological properties including antitumor activity. The aim of this study is to investigate the antitumor activity of ponicidin on the human cervical cancer HeLa cell line and the mechanism through which ponicidin exerts its antitumor effect. Cell viability was assessed by MTT assay. Cell apoptosis and the apoptosis-related activation in HeLa cells were evaluated by flow cytometry and western blot analysis. The results demonstrated that ponicidin treatment inhibited the proliferation of HeLa cells and induced cell apoptosis in a dose-dependent manner. The apoptosis induced by ponicidin was evidenced by Bcl-2/Bax dysregulation, cleavage of caspase-3, -9 and PARP. In addition, ponicidin treatment decreased the phosphorylation of Akt, while LY294002 pretreatment promoted the dephosphorylation of Akt and cell death induced by ponicidin. Furthermore, ponicidin treatment increased the phosphorylation of ERK1/2, JNK1/2 and p38 MAPK, while cell apoptosis was significantly attenuated when cells were co-treated with ponicidin and pharmacologic inhibitors U0126 (ERK1/2 kinase inhibitor), SP600125 (JNK kinase inhibitor) and SB202190 (p38 kinase inhibitor). In conclusion, ponicidin treatment induced apoptosis in HeLa cells through PI3K/Akt and MAPK signaling pathways and ponicidin may be a promising option in the treatment of cervical cancer.