| Abstract
| - Propolis, a natural product collected by honeybee, has been reported to exert a wide spectrum ofbiological functions. In this study, we have isolated a novel component, namely, propolin H, andinvestigated its effects in human carcinoma cells. Propolin H inhibited the proliferation of human lungcarcinoma cell lines in MTT assay, and a significant G1 arrest was observed to occur in a dose-dependent manner at 24 h of exposure in H460 cells. After treatment with propolin H in H460 cells,the content of the CDK inhibitor p21Waf1/Cip1 protein increased in correlation with the elevation in p53levels. Western blot analysis of G1 regulatory proteins further revealed a decrease in cyclin-dependentkinase 2 (CDK2) and CDK4 and an increase in cyclin E. The CDKs kinase activities assay showedthat propolin H has inhibited CDK2 and CDK4 kinase activities. Accordingly, coimmunoprecipitationsrevealed an increased association of both CDK2 and CDK4 immunoreactive protein with the p21Waf1/Cip1protein complex under propolin H-treated conditions. Additionally, we found that propolin H enhancedthe expression of p21Waf1/Cip1 in p53-mutant and p53-null lung carcinoma cell lines, following theinduction of G1 arrest. Together, these findings suggest that the induction of p21Waf1/Cip1 expressionoccurred through p53-dependent and -independent pathways in propolin H-treated cells. Propolin Hexerts its significantly growth inhibitory effects and may have therapeutic applications. Keywords: Propolis; propolin H; lung carcinoma cell; cell cycle; p21Waf1/Cip1
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