Oncotarget

Research Papers:

NPC-26 kills human colorectal cancer cells via activating AMPK signaling

Zhen Zhao, Li Feng, Jiqin Wang, Deshan Cheng, Mei Liu, Meirong Ling, Weiping Xu and Keyu Sun _

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Oncotarget. 2017; 8:18312-18321. https://doi.org/10.18632/oncotarget.15436

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Abstract

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

*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.


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