Cordycepin causes p21WAF1-mediated G2/M cell-cycle arrest by regulating c-Jun N-terminal kinase activation in human bladder cancer cells.
Cordycepin (3'-deoxyadenosine), a bioactive compound of Cordyceps militaris, has many pharmacological activities. The present study reveals novel molecular mechanisms for the anti-tumor effects of cordycepin in two different bladder cancer cell lines, 5637 and T-24 cells. Cordycepin treatment, at a dose of 200 microM (IC(50)) during cell-cycle progression resulted in significant and dose-dependent growth inhibition, which was largely due to G2/M-phase arrest, and resulted in an up-regulation of p21WAF1 expression, independent of the p53 pathway. Moreover, treatment with cordycepin-induced phosphorylation of JNK (c-Jun N-terminal kinases). Blockade of JNK function using SP6001259 (JNK-specific inhibitor) and small interfering RNA (si-JNK1) rescued cordycepin-dependent p21WAF1 expression, inhibited cell growth, and decreased cell cycle proteins. These results suggest that cordycepin could be an effective treatment for bladder cancer.
Lee
Se-Jung
SJ
Department of Food and Biotechnology, Chungju National University, Chungju, Chungbuk 380-702, South Korea.
Kim
Si-Kwan
SK
Choi
Won-Seok
WS
Kim
Wun-Jae
WJ
Moon
Sung-Kwon
SK
D000873:Anthracenes / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects* / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D003839:Deoxyadenosines / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology
D000873:Anthracenes; D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D003839:Deoxyadenosines; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases; C058120:cordycepin