Icilin inhibits E2F1-mediated cell cycle regulatory programs in prostate cancer.

Abstract

Aberrant expression of cell cycle regulators have been implicated in prostate cancer development and progression. Therefore, understanding transcriptional networks controlling the cell cycle remain a challenge in the development of prostate cancer treatment. In this study, we found that icilin, a super-cooling agent, down-regulated the expression of cell cycle signature genes and caused G1 arrest in PC-3 prostate cancer cells. With reverse-engineering and an unbiased interrogation of a prostate cancer-specific regulatory network, master regulator analysis discovered that icilin affected cell cycle-related transcriptional modules and identified E2F1 transcription factor as a target master regulator of icilin. Experimental analyses confirmed that icilin reduced the activity and expression levels of E2F1. These results demonstrated that icilin inactivates a small regulatory module controlling the cell cycle in prostate cancer cells. Our study might provide insight into the development of cell cycle-targeted cancer therapeutics.

• Authors: Sanghoon Lee, Jung Nyeo Chun, Su-Hwa Kim, Insuk So, Ju-Hong Jeon
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 441 Issue 4 Pg. 1005-10 (Nov 29 2013) ISSN: 1090-2104 [Electronic] United States
• PMID: 24239550 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• DNA, Superhelical
• E2F1 Transcription Factor
• Pyrimidinones
• icilin

Topics

• Cell Cycle (drug effects, genetics)
• Cell Line, Tumor
• DNA, Superhelical (drug effects)
• E2F1 Transcription Factor (antagonists & inhibitors)
• Humans
• Male
• Prostatic Neoplasms (genetics, pathology)
• Pyrimidinones (pharmacology)