Mitochondrial ROS contribute to oridonin-induced HepG2 apoptosis through PARP activation.

Oridonin, the main active constituent of , is known to exert antitumor activity via the induction of apoptosis in numerous types of human cancer cells. However, the underlying regulatory mechanisms of mitochondrial ROS in oridonin-induced HepG2 apoptosis remain largely unknown, due to limitations of subcellular imaging resolution. Previously, it has been suggested that mitochondria serve a potential role in sensing and signaling cellular redox changes in vital biological processes such as cell death and the abiotic stress response, based on studies involving the mitochondrial-targeted redox-sensitive green fluorescent protein (GFP). To address this, a mitochondrial-targeted Grx1-roGFP2 (mtGrx1-roGFP2) biosensor was implemented to monitor real-time mitochondrial redox changes of HepG2 cells in response to either HO/DTT or oridonin/SS31 treatment. It was determined that oridonin caused a perturbation in mitochondrial redox status, which in turn contributed to oridonin-induced apoptosis. Furthermore, a novel mechanism underlying the regulation of mitochondrial redox changes in oridonin-induced HepG2 apoptosis, presumably dependent on PARP cleavage, was proposed. In conclusion, the present study provides evidence in support of mitochondrial redox changes as a potential mediator in the apoptotic activities of oridonin in HepG2 cells, which provides insight into the molecular mechanisms by which mitochondrial redox signaling regulates oridonin-induced apoptosis in cancer therapy, and the development of mitochondria-specific oridonin as a promising novel anticancer therapeutic strategy.