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Propolin H from Taiwanese propolis induces G1 arrest in human lung carcinoma cells.

Abstract
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.
AuthorsMeng-Shih Weng, Chiung-Ho Liao, Chia-Nan Chen, Chia-Li Wu, Jen-Kun Lin
JournalJournal of agricultural and food chemistry (J Agric Food Chem) Vol. 55 Issue 13 Pg. 5289-98 (Jun 27 2007) ISSN: 0021-8561 [Print] United States
PMID17530771 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Flavanones
  • Monoterpenes
  • propolin H
  • Propolis
  • Cyclin-Dependent Kinases
Topics
  • Cell Division (drug effects)
  • Cell Line, Tumor
  • Cyclin-Dependent Kinases (antagonists & inhibitors)
  • Flavanones (isolation & purification, pharmacology)
  • G1 Phase (drug effects)
  • Humans
  • Lung Neoplasms (pathology)
  • Monoterpenes (isolation & purification, pharmacology)
  • Propolis (chemistry)
  • Taiwan

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