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• W2589744559 abstract "// Zhen Zhao 1, * , Li Feng 2, * , Jiqin Wang 3 , Deshan Cheng 3 , Mei Liu 3 , Meirong Ling 3 , Weiping Xu 4 , Keyu Sun 3 1 Clinical Laboratory, Minhang Hospital, Fudan University, Shanghai, China 2 Department of Gastroenterology, Minhang Hospital, Fudan University, Shanghai, China 3 Emergency Department, Minhang Hospital, Fudan University, Shanghai, China 4 Shanghai University of Medicine & Health Sciences, Shanghai, China * Co-first authors Correspondence to: Keyu Sun, email: sunkeyulunwen@163.com , sunkeyu539@126.com Weiping Xu, email: weipingxulunwen@163.com Keywords: NPC-26, colorectal cancer, AMP-activated protein kinase (AMPK), mitochondrion, cell death Received: December 01, 2016      Accepted: January 11, 2017      Published: February 17, 2017 ABSTRACT NPC-26 is novel mitochondrion-interfering compound. The current study tested its potential effect against colorectal cancer (CRC) cells. We demonstrated that NPC-26 induced potent anti-proliferative and cytotoxic activities against CRC cell lines (HCT-116, DLD-1 and HT-29). Activation of AMP-activated protein kinase (AMPK) signaling mediated NPC-26-induced CRC cell death. AMPKα1 shRNA knockdown or dominant negative mutation abolished NPC-26-induced AMPK activation and subsequent CRC cell death. NPC-26 disrupted mitochondrial function, causing mitochondrial permeability transition pore (mPTP) opening and reactive oxygen species (ROS) production. ROS scavengers (NAC or MnTBAP) and mPTP blockers (cyclosporin A or sanglifehrin A) blocked NPC-26-induced AMPK activation and attenuated CRC cell death. Significantly, intraperitoneal injection of NPC-26 potently inhibited HCT-116 tumor growth in severe combined immuno-deficient (SCID) mice. Yet, its anti-tumor activity was significantly weakened against AMPKα1-silenced HCT-116 tumors. Together, we conclude that NPC-26 kills CRC cells possibly via activating AMPK signaling." @default.
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• W2589744559 date "2017-02-17" @default.
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• W2589744559 title "NPC-26 kills human colorectal cancer cells via activating AMPK signaling" @default.
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• W2589744559 doi "https://doi.org/10.18632/oncotarget.15436" @default.
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