J Cancer 2020; 11(20):5900-5910. doi:10.7150/jca.46556

Research Paper

Propranolol induced apoptosis and autophagy via the ROS/JNK signaling pathway in Human Ovarian Cancer

Shujun Zhao1,2, Suzhen Fan1, Yanyu Shi1, Hongyan Ren1, Hanqing Hong1, Xiang Gao1, Min Zhang1, Qiaohong Qin1, Hongyu Li1,2✉

1. Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, No.7 Kangfuqian Street, Zhengzhou, 450000, P.R.China.
2. Zhengzhou Key Laboratory of Gynecological Oncology, 450052 Zhengzhou, China.

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Zhao S, Fan S, Shi Y, Ren H, Hong H, Gao X, Zhang M, Qin Q, Li H. Propranolol induced apoptosis and autophagy via the ROS/JNK signaling pathway in Human Ovarian Cancer. J Cancer 2020; 11(20):5900-5910. doi:10.7150/jca.46556. Available from https://www.jcancer.org/v11p5900.htm

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Propranolol has a significant anti-cancer effect towards various cancers. Our study aimed at investigating the underlying mechanism of Propranolol's therapeutic effect towards ovarian cancer. Specifically, Propranolol significantly reduced the viability of human ovarian cancer cell lines SKOV-3 and A2780 in a dose- and time-dependent manner. Flow cytometry analysis revealed that Propranolol induced the cell cycle arrest at G2/M phase therefore leading to apoptosis. Moreover, autophagy inhibitor 3-MA markedly enhanced the Propranolol-induced apoptosis. In addition, reactive oxygen species (ROS) increased dramatically after Propranolol treatment and Propranolol activated the phosphorylation of JNK. What is more, p38 inhibitor SB203580 and JNK inhibitor SP600125 attenuated the upregulated expression of LC3-II and cleaved-caspase-3 by the effect of Propranolol. ROS exclusive inhibitor antioxidant N-acetyl cysteine (NAC) weakens the phosphorylation of JNK proteins induced by Propranolol. In summary, these results suggested that Propranolol induced cell apoptosis and protective autophagy through the ROS/JNK signaling pathway in human ovarian cancer cells.

Keywords: Propranolol, Cell apoptosis, Autophagy, ROS/JNK signaling pathway, Ovarian cancer