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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 14, 2016; 22(10): 2900-2905
Published online Mar 14, 2016. doi: 10.3748/wjg.v22.i10.2900
Update on a tumor-associated NADH oxidase in gastric cancer cell growth
Hsiao-Ling Cheng, Yi-Hui Lee, Tein-Ming Yuan, Shi-Wen Chen, Pin-Ju Chueh
Hsiao-Ling Cheng, Yi-Hui Lee, Pin-Ju Chueh, Institute of Biomedical Sciences, National Chung Hsing University, Taichung 40227, Taiwan
Tein-Ming Yuan, Shi-Wen Chen, Department of Surgery, Feng-Yuan Hospital, Ministry of Health and Welfare, Taichung 42055, Taiwan
Pin-Ju Chueh, Graduate Institute of Basic Medicine, China Medical University, Taichung 40402, Taiwan
Pin-Ju Chueh, Department of Medical Research, China Medical University Hospital, Taichung 40402, Taiwan
Pin-Ju Chueh, Department of Biotechnology, Asia University, Taichung 41354, Taiwan
Author contributions: Cheng HL and Lee YH performed experiments; Cheng HL, Lee YH, Yuan TM, Chen SW and Chueh PJ participated in writing, editing, and reviewing of this manuscript.
Supported by the Ministry of Health and Welfare, Feng Yuan Hospital Research Project 103-004; and the National Science Council, No. NSC 100-2320-B-005-005 and No. NSC 101-2320-B-005-003.
Conflict-of-interest statement: The authors have no conflict of interest to declare.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Pin-Ju Chueh, PhD, Institute of Biomedical Sciences, National Chung Hsing University, Taichung 40227, Taiwan. pjchueh@dragon.nchu.edu.tw
Telephone: +886-4-22840896 Fax: +886-4-22853469
Received: April 29, 2015
Peer-review started: May 8, 2015
First decision: August 26, 2015
Revised: September 8, 2015
Accepted: November 9, 2015
Article in press: November 9, 2015
Published online: March 14, 2016
Abstract

Gastric cancer is one of the most common human malignancies, and its prevalence has been shown to be well-correlated with cancer-related deaths worldwide. Regrettably, the poor prognosis of this disease is mainly due to its late diagnosis at advanced stages after the cancer has already metastasized. Recent research has emphasized the identification of cancer biomarkers in the hope of diagnosing cancer early and designing targeted therapies to reverse cancer progression. One member of a family of growth-related nicotinamide adenine dinucleotide (NADH or hydroquinone) oxidases is tumor-associated NADH oxidase (tNOX; ENOX2). Unlike its counterpart CNOX (ENOX1), identified in normal rat liver plasma membranes and shown to be stimulated by growth factors and hormones, tNOX activity purified from rat hepatoma cells is constitutively active. Its activity is detectable in the sera of cancer patients but not in those of healthy volunteers, suggesting its clinical relevance. Interestingly, tNOX expression was shown to be present in an array of cancer cell lines. More importantly, inhibition of tNOX was well correlated with reduced cancer cell growth and induction of apoptosis. RNA interference targeting tNOX expression in cancer cells effectively restored non-cancerous phenotypes, further supporting the vital role of tNOX in cancer cells. Here, we review the regulatory role of tNOX in gastric cancer cell growth.

Keywords: Apoptosis, Capsaicin, Gastric cancer cells, Protein expression, Tumor-associated NADH oxidase

Core tip: Gastric cancer is one of the most common human malignancies, and its prevalence has been shown to be well-correlated with cancer-related deaths worldwide. Here, we review the role of tumor-associated NADH oxidase tNOX (ENOX2) in cancer, in particular its regulation of gastric cancer cell growth. The most common inhibitors of tNOX and the phenotypes associated with tNOX depletion are also discussed.