Oncotarget

Research Papers:

Capsazepine inhibits JAK/STAT3 signaling, tumor growth, and cell survival in prostate cancer

Jong Hyun Lee, Chulwon Kim, Seung Ho Baek, Jeong-Hyeon Ko, Seok Geun Lee, Woong Mo Yang, Jae-Young Um, Gautam Sethi _ and Kwang Seok Ahn

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Oncotarget. 2017; 8:17700-17711. https://doi.org/10.18632/oncotarget.10775

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Abstract

Jong Hyun Lee1, Chulwon Kim1, Seung Ho Baek1, Jeong-Hyeon Ko1, Seok Geun Lee1, Woong Mo Yang1, Jae-Young Um1, Gautam Sethi2, Kwang Seok Ahn1

1College of Korean Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea

2Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597

Correspondence to:

Gautam Sethi, email: phcgs@nus.edu.sg

Kwang Seok Ahn, email: ksahn@khu.ac.kr

Keywords: capsazepine, STAT3, PTPε, apoptosis, prostate cancer

Received: January 6, 2016     Accepted: July 14, 2016     Published: July 22, 2016

ABSTRACT

Persistent STAT3 activation is seen in many tumor cells and promotes malignant transformation. Here, we investigated whether capsazepine (Capz), a synthetic analogue of capsaicin, exerts anticancer effects by inhibiting STAT3 activation in prostate cancer cells. Capz inhibited both constitutive and induced STAT3 activation in human prostate carcinoma cells. Capz also inhibited activation of the upstream kinases JAK1/2 and c-Src. The phosphatase inhibitor pervanadate reversed Capz-induced STAT3 inhibition, indicating that the effect of Capz depends on a protein tyrosine phosphatase. Capz treatment increased PTPε protein and mRNA levels. Moreover, siRNA-mediated knockdown of PTPε reversed the Capz-induced induction of PTPε and inhibition of STAT3 activation, indicating that PTPε is crucial for Capz-dependent STAT3 dephosphorylation. Capz also decreased levels of the protein products of various oncogenes, which in turn inhibited proliferation and invasion and induced apoptosis. Finally, intraperitoneal Capz administration decreased tumor growth in a xenograft mouse prostate cancer model and reduced p-STAT3 and Ki-67 expression. These data suggest that Capz is a novel pharmacological inhibitor of STAT3 activation with several anticancer effects in prostate cancer cells.


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