Propolis, a
natural product collected by honeybee, has been reported to exert a wide spectrum of
biological functions. In this study, we have isolated a novel component, namely,
propolin H, and investigated its effects in human
carcinoma cells.
Propolin H inhibited the proliferation of human lung
carcinoma 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 p53 levels. Western blot analysis of G1 regulatory
proteins further revealed a decrease in
cyclin-dependent kinase 2 (CDK2) and CDK4 and an increase in
cyclin E. The CDKs
kinase activities assay showed that
propolin H has inhibited CDK2 and CDK4
kinase activities. Accordingly, coimmunoprecipitations revealed an increased association of both CDK2 and CDK4 immunoreactive
protein with the p21Waf1/Cip1
protein complex under
propolin H-treated conditions. Additionally, we found that
propolin H enhanced the expression of p21Waf1/Cip1 in p53-mutant and p53-null lung
carcinoma cell lines, following the induction of G1 arrest. Together, these findings suggest that the induction of p21Waf1/Cip1 expression occurred through p53-dependent and -independent pathways in
propolin H-treated cells.
Propolin H exerts its significantly growth inhibitory effects and may have therapeutic applications.