Oridonin induces G2/M cell cycle arrest and apoptosis through MAPK and p53 signaling pathways in HepG2 cells

Abstract

Abstract. Oridonin, the main active constituent of Isodon rubescen, has antihepatocarcinoma activity in experimental and clinical settings. The aims of the study were to explore the anticancer effect of oridonin in HepG2 cells and to investigate the underlying mechanisms. Results showed that oridonin treatment for 24 or 48 h resulted in a marked decrease in cell viability time-and dose-dependently. IC 50 values were determined as 38.86 μM and 24.90 μM for 24-h and 48-h treatments, respectively. Flow cytometric analysis showed that a 24-h treatment of 40 μM oridonin induced G2/M cell cycle arrest and apoptosis. Typical apoptotic nucleus alterations were observed with fluorescence microscope after DAPI staining. Immunoblot analysis demonstrated that oridonin treatment increased expression levels of p-JNK, p-p38, p-p53 and p21, elevated the level of cyclin B1/p-Cdc2 (Tyr15) complex, and inhibited the expression of p-ERK. Moreover, oridonin treatment activated caspase-9 and caspase-3. In conclusion, oridonin induced G2/M cell cycle arrest and apoptosis in HepG2 cells through MAPK and p53 pathways, which advances our understanding on the molecular mechanisms of oridonin in hepatocarcinoma management.

Oridonin from Rabdosia rubescens: An emerging potential in cancer therapy – A comprehensive review

“…Investigations reported that ORI induces phase G2/M cell cycle arrest and apoptosis in human hepatoma (HepG2) cells through the alteration of MAPK and p53 metabolic pathways (Wang et al, 2010). Another study indicated that upregulation of Glycyl-tRNA synthetase and heterochromatin protein 1 beta might facilitate inhibitory effects of ORI on tyrosine kinase and telomerase, respectively, in HepG2 cells (Wang, Ye, Pan, et al, 2011).…”

Progress of natural sesquiterpenoids in the treatment of hepatocellular carcinoma

“…Administration with germacrone could increase the production of ROS, following by promoted cleavage of caspase 3 and gasdermin E, thereby promoting pyroptosis of HepG2 cells. Furanodiene ( 24 ) is another active sesquiterpenoid from Ezhu and could induce HepG2 cell arrest at G2/M and apoptosis ( 47 ). The apoptosis induction effect of furanodiene was achieved by activating mitochondrial signaling pathway, including promoting mitochondrial transmembrane depolarization, release of mitochondrial cytochrome c and cleavage of PARP, and activating caspases−3.…”