Inhibitory effect of acetyl-11-keto-beta-boswellic acid on androgen receptor by interference of Sp1 binding activity in prostate cancer cells.

Abstract

Androgen receptor (AR)-mediated signaling is crucial for the development and progression of prostate cancer (PCa). Naturally occurring phytochemicals that target the AR signaling offer significant protection against this disease. Acetyl-11-keto-beta-boswellic acid (AKBA), a compound isolated from the gum-resin of Boswellia carterii, caused G1-phase cell cycle arrest with an induction of p21(WAF1/CIP1), and a reduction of cyclin D1 as well in prostate cancer cells. AKBA-mediated cellular proliferation inhibition was associated with a decrease of AR expression at mRNA and protein levels. Furthermore, the functional biomarkers used in evaluation of AR transactivity showed suppressions of prostate-specific antigen promoter-dependent and androgen responsive element-dependent luciferase activities. Additionally, down-regulation of an AR short promoter mainly containing a Sp1 binding site suggested the essential role of Sp1 for the reduction of AR expression in cells exposed to AKBA. Interruption effect of AKBA on Sp1 binding activity but not Sp1 protein levels was further confirmed by EMSA and transient transfection with a luciferase reporter driven by three copies of the Sp1 binding site of the AR promoter. Therefore, anti-AR properties ascribed to AKBA suggested that AKBA-containing drugs could be used for the development of novel therapeutic chemicals.

• Authors: Hui-Qing Yuan, Feng Kong, Xiao-Ling Wang, Charles Y F Young, Xiao-Yan Hu, Hong-Xiang Lou
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 75 Issue 11 Pg. 2112-21 (Jun 01 2008) ISSN: 1873-2968 [Electronic] England
• PMID: 18430409 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Androgen Receptor Antagonists
• Sp1 Transcription Factor
• Triterpenes
• acetyl-11-ketoboswellic acid
• DNA

Topics

• Androgen Receptor Antagonists
• Cell Line, Tumor
• DNA (metabolism)
• G1 Phase (drug effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Male
• Prostatic Neoplasms (drug therapy, metabolism)
• Protein Binding
• Sp1 Transcription Factor (drug effects, metabolism)
• Triterpenes (pharmacology)