Artesunate induces autophagy dependent apoptosis through upregulating ROS and activating AMPK-mTOR-ULK1 axis in human bladder cancer cells. (1st November 2020)

• Record Type: Journal Article
• Authors: Zhou, Xuejian; Chen, Yu; Wang, Feifan; Wu, Hongshen; Zhang, Yan; Liu, Jiaxin; Cai, Yueshu; Huang, Shihan; He, Ning; Hu, Zhenghui; Jin, Xiaodong
• Is Part Of: Chemico-biological interactions. Volume 331(2020)
• Publication Date: 2020-11-01
• Subjects: Artesunate -- Bladder cancer -- ROS -- Autophagy -- Apoptosis -- AMPK-mTOR-ULK1; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2020.109273
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: Artesunate is a kind of derivative of artemisinin, which possesses potent anti-cancer effect in addition to its anti-malarial property. And autophagy was a highly conserved process, exerting a double-edged effect in cancer cell survival. Besides, apoptosis is a programmed cell death program, crucial to cell homeostasis. However, the relations between autophagy and apoptosis, and the role of artesunate in this interaction have not been elucidated in bladder cancer. In present study, we used human bladder cancer cells (T24 and EJ cell lines) to investigate that how artesunate would influence autophagy and apoptosis processes. We found that artesunate could inhibit the viability, proliferation and migration of bladder cancer cells, as well as induce autophagy in a time and dose dependent manner, in addition, the artesunate induced autophagy subsequently activated cells apoptosis. Furthermore, we pretreated T24 and EJ cells with 3-Methyladenine or Rapamycin to inhibit or promote autophagy, respectively, leading to inhibited or increased apoptosis. Moreover, pretreatment of these cell lines with Acadesine or Dorsomorphin to activate or inhibit the AMPK-mTOR-ULK1 pathway, respectively, also resulting in promotion or suppression in both autophagy and apoptosis. In the upstream, ROS upregulation triggered by ART initiated AMPK-mTOR-ULK1 axis. However, this initiative effect of ROS can be reversed by N-Acetyl-l -cysteine. Therefore, this study indicated that Artesunate induces autophagy dependent apoptosis through upregulating ROS and activating AMPK-mTOR-ULK1 pathway in human bladder cancer cells. Highlights: Artesunate induce caspase dependent apoptosis in human bladder cancer cells. Artesunate time and dose dependently activated autophagy in human bladder cancer cells. Apoptosis in human bladder cancer cells were induced by artesunate activated autophagy. AMPK-mTOR-ULK1 pathway mediated artesunate induced autophagy dependent apoptosis in human bladder cancer cells. ROS plays a vital role in ART activated AMPK-mTOR-ULK1 pathway.