Apoptosis induction of human prostate carcinoma cells by cordycepin through reactive oxygen species-mediated mitochondrial death pathway

Abstract

Cordycepin is the main functional component of Cordyceps militaris, which has been widely used in oriental traditional medicine. This compound has been shown to possess many pharmacological properties, such as enhancing the body's immune function, and anti-inflammatory, anti-aging and anticancer effects. In the present study, we investigated the apoptotic effects of cordycepin in human prostate carcinoma cells. We found that treatment with cordycepin significantly inhibited cell growth by inducing apoptosis in PC-3 cells. Apoptosis induction of PC-3 cells by cordycepin showed correlation with proteolytic activation of caspase-3 and -9, but not caspase-8, and concomitant degradation of poly (ADP-ribose) polymerases, collapse of the mitochondrial membrane potential (MMP). In addition, cordycepin treatment resulted in an increase of the Bax/Bcl-2 (or Bcl-xL) ratio, downregulation of inhibitor of apoptosis protein (IAP) family members, Bax conformational changes, and release of cytochrome c from the mitochondria to the cytosol. The cordycepin-induced apoptosis was also associated with the generation of intracellular reactive oxygen species (ROS). However, the quenching of ROS generation with antioxidant N-acetyl-L-cysteine conferred significant protection against cordycepin-elicited ROS generation, disruption of the MMP, modulation of Bcl-2 and IAP family proteins, caspase-3 and -9 activation and apoptosis. This indicates that the cellular ROS generation plays a pivotal role in the initiation of cordycepin-triggered apoptotic death. Collectively, our findings suggest that cordycepin is a potent inducer of apoptosis of prostate cancer cells via a mitochondrial-mediated intrinsic pathway and that this agent may be of value in the development of a potential therapeutic candidate for both the prevention and treatment of cancer.

Cordycepin Induces Apoptosis and Inhibits Proliferation of Human Lung Cancer Cell Line H1975 via Inhibiting the Phosphorylation of EGFR

“…Liou et al [19] reported that cordycepin could suppress integrin/FAK signaling and the epithelial-mesenchymal transition in hepatocellular carcinoma. Lee and co-workers [20] suggested that cordycepin could inhibit the migration and invasion of LNCap human prostate carcinoma cells by inactivation of AKT, resulting in the down-regulation of the TJs (Tight Junctions) and MMPs (Matix Metalloproteinases). Chen and co-workers [21] investigated the effect of cordycepin on C6 glioma cells and showed that cordycepin could induce the apoptosis of C6 glioma cells via the adenosine 2A receptor-p53-caspase-7-PARP pathway.…”

Cordycepin increases sensitivity of Hep3B human hepatocellular carcinoma cells to TRAIL-mediated apoptosis by inactivating the JNK signaling pathway

“…This activity has been well described in vitro with purified RNA polymerases and poly(A) polymerases from a number of organisms, including yeasts and mammals (9,10). Cordycepin has anticancer activities including induction of apoptosis, DNA double-strand break activity, and cell cycle arrest in cancer cells (11)(12)(13)(14)(15). This compound also inhibits metastasis and angiogenesis (16)(17)(18)(19).…”

A Constitution Dependent QOL Assessment

“…In general, those drugs often anti-metabolites that interfere with nucleic acid or protein synthesis can suppress the immune response. The greatest problem facing the physician is to effectively balance at the same time the dosages of drugs or irradiation so that the immune system is suppressed against the graft, but is still capable of defense against environmental pathogens [32][33][34][35][36][37][38][39][40][41][42].…”