Carvacrol Alleviates Prostate Cancer Cell Proliferation, Migration, and Invasion through Regulation of PI3K/Akt and MAPK Signaling Pathways.

Yun Luo,Ning Na,Zhi Shi,Min-Hua Lu,Jin-Ming Di,Jie-Ying Wu

doi:10.1155/2016/1469693

Abstract

TRPM7 is a potential therapeutic target for treatment of prostate cancer. In this study, we investigated the effects of nonselective TRPM7 inhibitor carvacrol on cell proliferation, migration, and invasion of prostate cancer PC-3 and DU145 cells. Our results showed that carvacrol blocked TRPM7-like currents in PC-3 and DU145 cells and reduced their proliferation, migration, and invasion. Moreover, carvacrol treatment significantly decreased MMP-2, p-Akt, and p-ERK1/2 protein expression and inhibited F-actin reorganization. Furthermore, consistently, TRPM7 knockdown reduced prostate cancer cell proliferation, migration, and invasion as well. Our study suggests that carvacrol may have therapeutic potential for the treatment of prostate cancer through its inhibition of TRPM7 channels and suppression of PI3K/Akt and MAPK signaling pathways.

Highlights

Prostate cancer (PCa) is the second leading cause of cancerrelated death in men [1,2,3]
Inhibition of Transient receptor potential melastatin-like 7 channel (TRPM7) enhances TNF-related apoptosis inducing-ligand- (TRAIL-) induced apoptosis in PC-3 cells [12], indicating that TRPM7 contributes to the pathogenesis of prostate cancer and serves as a potential therapeutic target for prostate cancer [13]
We further evaluated the effects of carvacrol on TRPM7-like currents, proliferation, migration, and invasion in PC-3 and DU145 cells and investigated the potential underlying mechanisms involved in these effects

Summary

Introduction

Prostate cancer (PCa) is the second leading cause of cancerrelated death in men [1,2,3]. Increasing Ca2+ and Mg2+ influx promotes the proliferation of prostate cancer cells through activating TRPM7 [10]. Cholesterol activates TRPM7 and increases Ca2+ entry, regulating proliferation, migration, and viability of human prostate cells [11]. Several signaling pathways were reported to be regulated by TRPM7, including signal Transducer and Activator of Transcription 3 (STAT3), Notch, PI3K/Akt, and MAPK signaling pathways [14, 15]. Knockdown TRPM7 by shRNA inhibited cholesterol-induced Akt or ERK phosphorylation [11]. It suggests that both PI3K/Akt and MAPK signaling pathways are the downstream mechanisms of TRPM7 functions in prostate cancer

Methods

Results

Conclusion