Dioscin Promotes Prostate Cancer Cell Apoptosis and Inhibits Cell Invasion by Increasing SHP1 Phosphorylation and Suppressing the Subsequent MAPK Signaling Pathway

Shuyun He; Jinrui Yang; Shaobo Hong; Haijian Huang; Qingguo Zhu; Liefu Ye; Tao Li; Xing Zhang; Yongbao Wei; Yunliang Gao

doi:10.3389/fphar.2020.01099

Dioscin Promotes Prostate Cancer Cell Apoptosis and Inhibits Cell Invasion by Increasing SHP1 Phosphorylation and Suppressing the Subsequent MAPK Signaling Pathway

Front Pharmacol. 2020 Jul 24:11:1099. doi: 10.3389/fphar.2020.01099. eCollection 2020.

Authors

Shuyun He^{1

2}, Jinrui Yang¹, Shaobo Hong³, Haijian Huang⁴, Qingguo Zhu³, Liefu Ye³, Tao Li³, Xing Zhang⁵, Yongbao Wei^{1

3}, Yunliang Gao¹

Affiliations

¹ Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, China.
² Department of Urology, The People's Hospital of Xiangtan Country, Xiangtan, China.
³ Shengli Clinical Medical College of Fujian Medical University and Department of Urology, Fujian Provincial Hospital, Fuzhou, China.
⁴ Shengli Clinical Medical College of Fujian Medical University and Department of Pathology, Fujian Provincial Hospital, Fuzhou, China.
⁵ Department of Urology, The Traditional Chinese Medicine Hospital of Yangzhou, Yangzhou University of Traditional Chinese Medicine, Yangzhou, China.

Abstract

Dioscin possesses antioxidant effects and has anticancer ability in many solid tumors including prostate cancer (PCa). Nevertheless, its effect and mechanism of anti-PCa action remain unclear. The tyrosine protein phosphatase SHP1, which contains an oxidation-sensitive domain, has been confirmed as a target for multicancer treatment. Further studies are needed to determine whether dioscin inhibits PCa through SHP1. We performed in vitro studies using androgen-sensitive (LNCaP) and androgen-independent (LNCaP -C81) cells to investigate the anticancer effects and possible mechanisms of dioscin after administering interleukin-6 (IL-6) and dihydrotestosterone (DHT). Our results show that dioscin inhibited cell growth and invasion by increasing SHP1 phosphorylation [p-SHP1 (Y536)] and inhibiting the subsequent P38 mitogen-activated protein kinase signaling pathway. Further in vivo studies confirmed that dioscin promoted caspase-3 and Bad-related cell apoptosis in these two cell lines. Our research suggests that the anticancer effects of dioscin on PCa may occur through SHP1. Dioscin may be useful to treat androgen-sensitive and independent PCa in the future.

Keywords: SHP1; cell apoptosis; cell invasion; dioscin; mitogen-activated protein kinase; prostate cancer.