cytochrome-c-t and cordycepin

Cordycepin, or 3'‑deoxyadenosine, is a derivative of the nucleoside adenosine. Initially extracted from the fungus Cordyceps militaris, cordycepin exhibits antitumor activity against certain cancer cell lines; however, the mechanism by which cordycepin counteracts colorectal cancer (CRC) remains poorly understood. The aim of the present study was to explore the underlying mechanisms of cordycepin against human CRC. To investigate the molecular mechanisms of cordycepin against colon cancer and in driving apoptosis, p53 and Bcl‑2‑like protein 4‑null (Bax‑/‑) colon cancer HCT116 cell lines were used. Cell viability and growth were repressed in a dose‑dependent manner in cells treated with cordycepin. Treatment with cordycepin resulted in increased apoptosis in HCT116 cells; however, flow cytometic analysis demonstrated that apoptosis was notably decreased in the Bax‑/‑ HCT116 cell lines, but not in the p53‑/‑ HCT116 cell lines. Furthermore, cordycepin exposure resulted in the translocation of Bax from the cytosol to the mitochondria and the subsequent release of cytochrome c from the mitochondria. Results from the present study demonstrated that cordycepin inhibited colon cancer cell growth in vitro and this appears to be through the endogenous Bax‑dependent mitochondrial apoptosis pathway, which suggested a molecular mechanism for cordycepin against human colon cancer. These results indicated the possibility of cordycepin as a novel drug for the prevention of colon cancer.

Topics: Apoptosis; bcl-2-Associated X Protein; Cell Line, Tumor; Cell Proliferation; Cell Survival; Colorectal Neoplasms; Cytochromes c; Deoxyadenosines; HCT116 Cells; Humans; Mitochondria; Tumor Suppressor Protein p53

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.

Topics: Acetylcysteine; Antineoplastic Agents; Apoptosis; bcl-2-Associated X Protein; bcl-X Protein; Caspase 3; Caspase 8; Caspase 9; Cell Line, Tumor; Cytochromes c; Deoxyadenosines; Down-Regulation; Enzyme Activation; Humans; Inhibitor of Apoptosis Proteins; Male; Membrane Potential, Mitochondrial; Mitochondria; Poly(ADP-ribose) Polymerases; Prostatic Neoplasms; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species