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.

• Authors: Hye Hyeon Lee, Cheol Park, Jin-Woo Jeong, Min Jeong Kim, Min Jeong Seo, Byoung Won Kang, Jeong Uck Park, Gi-Young Kim, Byung Tae Choi, Yung Hyun Choi, Yong Kee Jeong
• Journal: International journal of oncology (Int J Oncol) Vol. 42 Issue 3 Pg. 1036-44 (Mar 2013) ISSN: 1791-2423 [Electronic] Greece
• PMID: 23292300 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Deoxyadenosines
• Inhibitor of Apoptosis Proteins
• Proto-Oncogene Proteins c-bcl-2
• Reactive Oxygen Species
• bcl-2-Associated X Protein
• bcl-X Protein
• Cytochromes c
• Poly(ADP-ribose) Polymerases
• Caspase 3
• Caspase 8
• Caspase 9
• cordycepin
• Acetylcysteine

Topics

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