Propolin H from Taiwanese propolis induces G1 arrest in human lung carcinoma cells.
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.
Weng
Meng-Shih
MS
Graduate Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei 10018, Taiwan.
Liao
Chiung-Ho
CH
Chen
Chia-Nan
CN
Wu
Chia-Li
CL
Lin
Jen-Kun
JK
D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D044950:Flavanones / Q000302:isolation & purification / Q000494:pharmacology*; D016193:G1 Phase / Q000187:drug effects*; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D039821:Monoterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D011429:Propolis / Q000737:chemistry*; D013624:Taiwan
D044950:Flavanones; D039821:Monoterpenes; C521817:propolin H; D011429:Propolis; D018844:Cyclin-Dependent Kinases