2. Academic Validation
  3. Alkannin induces cytotoxic autophagy and apoptosis by promoting ROS-mediated mitochondrial dysfunction and activation of JNK pathway

Alkannin induces cytotoxic autophagy and apoptosis by promoting ROS-mediated mitochondrial dysfunction and activation of JNK pathway

  • Biochem Pharmacol. 2020 Oct;180:114167. doi: 10.1016/j.bcp.2020.114167.
Qianwen Zheng 1,  Qin Li 1,  Gang Zhao 1,  Jie Zhang 1,  Hang Yuan 1,  Di Gong 1,  Yafei Guo 1,  Xinhua Liu 2,  Kai Li 3,  Ping Lin 4
Affiliations

Affiliations

  • 1 Lab of Experimental Oncology, State Key Laboratory of Biotherapy and Cancer Center, and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
  • 2 School of Pharmacy, Anhui Medical University, Hefei 230032, China. Electronic address: xhliuhx@163.com.
  • 3 Lab of Experimental Oncology, State Key Laboratory of Biotherapy and Cancer Center, and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China. Electronic address: cupidkai.4444@163.com.
  • 4 Lab of Experimental Oncology, State Key Laboratory of Biotherapy and Cancer Center, and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China. Electronic address: linping@scu.edu.cn.
PMID: 32702370 DOI: 10.1016/j.bcp.2020.114167
Abstract

Naphthoquinone derivatives and metabolites are widely dispersed molecules in nature. Alkannin, a natural naphthoquinone compound, induces excellent cytotoxicity in Cancer cells. However, the detailed mechanism by which alkannin inhibits Cancer cell survival remains unclear. In the present study, we isolated alkannin from Arnebia euchroma and found that alkannin induced cytotoxic Autophagy and Apoptosis in many types of Cancer cells in a dose-dependent manner. Alkannin treatment resulted in elevated accumulation of intracellular Reactive Oxygen Species (ROS), leading to mitochondrial membrane potential loss, oxidative damage and JNK and p38 MAPK pathway activation. Notably, we found an antagonistic pattern of p38 MAPK and JNK signaling in the regulation of alkannin-mediated Apoptosis and Autophagy. Antioxidant NAC effectively attenuated alkannin-induced cytotoxicity and activation of downstream signaling pathways. Moreover, alkannin enhanced the sensitivity of Cancer cells to chemotherapeutic agents. In summary, our study highlights the significant broad-spectrum antitumor effects of alkannin and reveals an important mechanism by which alkannin induces cytotoxic Autophagy and Apoptosis by promoting ROS-mediated mitochondrial dysfunction and activation of the JNK pathway.

Keywords

Alkannin; Apoptosis; Cytotoxic autophagy; JNK pathway; Reactive oxygen species.

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