Oridonin induces apoptosis via PI3K/Akt pathway in cervical carcinoma HeLa cell line

Abstract

Aim: To investigate the apoptosis-inducing effect of oridonin, a diterpenoid isolated from Rabdosia rubescens, in the human cervical carcinoma HeLa cell line. Methods: A morphological analysis, nuclear condensation, and fragmentation of chromatin were monitored using Hoechst 33342 staining. Cell viability was assessed using the 3-(4, 5-dimethylthiazol-(2)-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. Cell apoptosis and the apoptosis-related activation in the HeLa cell line were evaluated by flow cytometry and Western blotting. Results: Oridonin suppressed the proliferation of the HeLa cell line in a dose-and time-dependent fashion. Oridonin treatment downregulated the activation of protein kinase B (Akt), the expression of forkhead box class O (FOXO) transcription factor, and glycogen synthase kinase 3 (GSK3). Oridonin also induced the release of cytochrome c accompanied by the activation of caspase-3 and poly-adenosine diphosphate-ribose polymerase cleavage. In addition, Z-D(OMe)-E(OMe)-V-D(OMe)-FMK (z-DEVD-fmk), an inhibitor of caspases, prevented caspase-3 activation and abrogated oridonin-induced cell death. Finally, oridonin treatment of the HeLa cell line downregulated the expression of the inhibitor of the apoptosis protein. Conclusion:Our results showed that oridonin-induced apoptosis involved several molecular pathways. Oridonin may suppress constitutively activated targets of phosphatidylinositol 3-kinase (Akt, FOXO, and GSK3) in the HeLa cell line, inhibiting the proliferation and induction of caspase-dependent apoptosis.

Oridonin induces G2/M cell cycle arrest and apoptosis via the PI3K/Akt signaling pathway in hormone-independent prostate cancer cells

“…There is substantial evidence to suggest that activation of the PI3K/Akt pathway is a common occurrence in advanced prostate cancer (31)(32)(33). It has previously been reported that PI3K/Akt is involved in oridonin-induced apoptosis in numerous cancer cells (34,35). The present results demonstrated that Akt is constitutively phosphorylated at Ser 473 sites in the 2 prostate cancer cells, and that oridonin may decrease the expression of PI3K p85 subunit and the phosphorylation of Akt at Ser 473 sites.…”

Oridonin inhibits the proliferation of human osteosarcoma cells by suppressing Wnt/β-catenin signaling

“…addition to MAPK signaling, ORI was reported to be able to inhibit proliferation and induce caspase-dependent apoptosis via downregulation of PI3K/Akt pathway in cervical carcinoma HeLa cell line (34). Treatment of prostate cancer cells with ORI also caused the upregulation of P21, autophagy and apotosis (35).…”

Oridonin triggers apoptosis in colorectal carcinoma cells and suppression of microRNA-32 expression augments oridonin-mediated apoptotic effects

“…Oridonin has been found to have various pharmacological and biological effects, such as anti-inflammatory, anti-viral, and anti-bacterial activities [11,12], but its anti-tumor effects have attracted considerable attention in recent years. Increasing studies have demonstrated that oridonin has cancer preventive and proapoptotic activities against various cancer cells, such as hepatocellular carcinoma cells [13], gastric cancer cells [14], oesophageal carcinoma cells [15], prostate cancer cells [16], cervical carcinoma cells [17], and colorectal cancer cells [18]. However, to our knowledge, the exact effects and the related mechanisms of oridonin against colorectal carcinoma cells remain largely unknown.…”