NPC-26 kills human colorectal cancer cells via activating AMPK signaling
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Zhen Zhao1,*, Li Feng2,*, Jiqin Wang3, Deshan Cheng3, Mei Liu3, Meirong Ling3, Weiping Xu4, Keyu Sun3
1Clinical Laboratory, Minhang Hospital, Fudan University, Shanghai, China
2Department of Gastroenterology, Minhang Hospital, Fudan University, Shanghai, China
3Emergency Department, Minhang Hospital, Fudan University, Shanghai, China
4Shanghai University of Medicine & Health Sciences, Shanghai, China
Weiping Xu, email: firstname.lastname@example.org
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
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.
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