Caffeic acid phenethyl ester induces E2F-1-mediated growth inhibition and cell-cycle arrest in human cervical cancer cells.

Abstract

Caffeic acid phenyl ester (CAPE) has been identified as an active component of propolis, a substance that confers diverse activities in cells of various origins. However, the molecular basis of CAPE-mediated cellular activity remains to be clarified. Here, we show that CAPE preferentially induced S- and G2 /M-phase cell-cycle arrests and initiated apoptosis in human cervical cancer lines. The effect was found to be associated with increased expression of E2F-1, as there is no CAPE-mediated induction of E2F-1 in the pre-cancerous cervical Z172 cells. CAPE also up-regulated the E2F-1 target genes cyclin A, cyclin E and apoptotic protease activating of factor 1 (Apaf-1) but down-regulated cyclin B and induced myeloid leukemia cell differentiation protein (Mcl-1). These results suggest the involvement of E2F-1 in CAPE-mediated growth inhibition and cell-cycle arrest. Transient transfection studies with luciferase reporters revealed that CAPE altered the transcriptional activity of the apaf-1 and mcl-1 promoters. Further studies using chromatin immunoprecipitation assays demonstrated that E2F-1 binding to the apaf-1 and cyclin B promoters was increased and decreased, respectively, in CAPE-treated cells. Furthermore, E2F-1 silencing abolished CAPE-mediated effects on cell-cycle arrest, apoptosis and related gene expression. Taken together, these results indicate a crucial role for E2F-1 in CAPE-mediated cellular activities in cervical cancer cells.

• Authors: Tzu-Hui Hsu, Chin-Chen Chu, Mei-Whey Hung, Hwei-Jen Lee, Hsien-Jun Hsu, Tsu-Chung Chang
• Journal: The FEBS journal (FEBS J) Vol. 280 Issue 11 Pg. 2581-93 (Jun 2013) ISSN: 1742-4658 [Electronic] England
• PMID: 23497083 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 The Authors Journal compilation © 2013 FEBS.

Chemical References

• Caffeic Acids
• Cytostatic Agents
• E2F1 Transcription Factor
• E2F1 protein, human
• caffeic acid phenethyl ester
• Phenylethyl Alcohol

Topics

• Apoptosis (drug effects, physiology)
• Caffeic Acids (pharmacology)
• Cell Cycle Checkpoints (drug effects, physiology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cytostatic Agents (pharmacology)
• E2F1 Transcription Factor (antagonists & inhibitors, genetics, physiology)
• Female
• Gene Knockdown Techniques
• HeLa Cells
• Humans
• Phenylethyl Alcohol (analogs & derivatives, pharmacology)
• Promoter Regions, Genetic
• Uterine Cervical Neoplasms (drug therapy, metabolism, pathology)