Cordycepin causes p21WAF1-mediated G2/M cell-cycle arrest by regulating c-Jun N-terminal kinase activation in human bladder cancer cells

Se-Jung Lee; Si-Kwan Kim; Won-Seok Choi; Wun-Jae Kim; Sung-Kwon Moon

doi:10.1016/j.abb.2009.09.001

Cordycepin causes p21WAF1-mediated G2/M cell-cycle arrest by regulating c-Jun N-terminal kinase activation in human bladder cancer cells

Arch Biochem Biophys. 2009 Oct 15;490(2):103-9. doi: 10.1016/j.abb.2009.09.001. Epub 2009 Sep 5.

Authors

Se-Jung Lee¹, Si-Kwan Kim, Won-Seok Choi, Wun-Jae Kim, Sung-Kwon Moon

Affiliation

¹ Department of Food and Biotechnology, Chungju National University, Chungju, Chungbuk 380-702, South Korea.

PMID: 19733546
DOI: 10.1016/j.abb.2009.09.001

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anthracenes / pharmacology
Antineoplastic Agents / pharmacology*
Cell Cycle / drug effects*
Cell Cycle / physiology
Cell Division / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
Deoxyadenosines / pharmacology*
Enzyme Activation / drug effects
G2 Phase / drug effects
Humans
JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
JNK Mitogen-Activated Protein Kinases / genetics
JNK Mitogen-Activated Protein Kinases / metabolism*
MAP Kinase Signaling System / drug effects
Protein Kinase Inhibitors / pharmacology
RNA, Small Interfering / genetics
Up-Regulation / drug effects
Urinary Bladder Neoplasms / drug therapy*
Urinary Bladder Neoplasms / metabolism*
Urinary Bladder Neoplasms / pathology

Substances

Anthracenes
Antineoplastic Agents
CDKN1A protein, human
Cyclin-Dependent Kinase Inhibitor p21
Deoxyadenosines
Protein Kinase Inhibitors
RNA, Small Interfering
pyrazolanthrone
JNK Mitogen-Activated Protein Kinases
cordycepin