We report here the widdrol, an odorous compound extracted from Juniperus chinensis, induced cell cycle arrest in human lung carcinoma A549 cells. We found the widdrol significantly induced cell-cycle arrest in G1 phase. To investigate the possible mechanisms, G1-related proteins were assayed by western blot analysis. Widdrol treatment resulted in the up-regulation of tumor suppressor p53 and cyclin-dependent kinase (CDK) inhibitor p21. In contrast, the expressions of cyclin-dependent kinase (CDK2), cyclin E, retinoblastoma protein (pRB) and proliferating cell nuclear antigen (PCNA) levels were markedly decreased in the concentration-dependent manner. Moreover, the minichromosome maintenance (MCM) proteins, highly expressed in cancer cells, were significantly down-regulated in A549 cells treated with widdrol. Overall, these observations suggest widdrol induces antiproliferation and arrest G1 phase in A549 cells, possibly mediated by the inhibition of the MCM protein expression. Consequently, widdrol is a potential candidate for the anticancer drug development. (Cancer Prev Res 14, 265-273, 2009)

Keywords: Widdrol, MCM protein, A549 cells, G1 arrest, CDK inhibitor