1. Academic Validation
  2. Palmatine induces G2/M phase arrest and mitochondrial-associated pathway apoptosis in colon cancer cells by targeting AURKA

Palmatine induces G2/M phase arrest and mitochondrial-associated pathway apoptosis in colon cancer cells by targeting AURKA

  • Biochem Pharmacol. 2020 May;175:113933. doi: 10.1016/j.bcp.2020.113933.
Xiaojiang Liu 1 Yaru Zhang 1 Siqi Wu 2 Minmin Xu 1 Youfeng Shen 2 Min Yu 1 Jinhua Fan 1 Sijia Wei 2 Chaohang Xu 2 Lu Huang 1 Han Zhao 1 Xuegang Li 3 Xiaoli Ye 4
Affiliations

Affiliations

  • 1 Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, Innovation, School of Life Sciences, Southwest University, Chongqing 400715, China.
  • 2 Chongqing Productivity Promotion Center of Chinese Traditional Medicine, Modernization, School of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China.
  • 3 Chongqing Productivity Promotion Center of Chinese Traditional Medicine, Modernization, School of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China. Electronic address: Xuegangli@swu.edu.cn.
  • 4 Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, Innovation, School of Life Sciences, Southwest University, Chongqing 400715, China. Electronic address: Xuegangli@swu.edu.cn.
Abstract

Studies have shown that palmatine (PAL) has anti-cancer effects. However, the activity and potential mechanisms of PAL against colorectal Cancer remain elusive. The results showed that PAL significantly inhibited the proliferation of colon Cancer cells in vitro and in vivo without significant effect on non-tumorigenic colon cells. Target prediction and clinical sample database analysis suggested that PAL may contribute to colon Cancer cells phase arrest and Apoptosis by targeting Aurora Kinase A (AURKA). Inhibition and overexpression of AURKA proved that PAL induces G2/M phase arrest and Apoptosis in colon Cancer cells by targeting AURKA. Moreover, PAL promoted intracellular Reactive Oxygen Species (ROS) production and decreased mitochondrial membrane potential (ΔΨm). PAL reduced the levels of AURKA, Bcl-xL and Bcl2 proteins, and promoted the expression of pro-apoptotic proteins P53, P73, Caspase3 and Caspase9, as well as the increase of cytochrome c (cyt. c) in cell lysates in vitro and in vivo. Together, our study confirmed that PAL induced G2/M phase arrest and mitochondrial-associated pathway Apoptosis in colon Cancer cells by targeting AURKA. PAL may provide a novel solution for the treatment of colon Cancer by serving as a new AURKA inhibitor.

Keywords

AURKA; Apoptosis; Colon cancer; Palmatine (PAL).

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