Tumor suppressor gene Oxidored-nitro domain-containing protein 1 regulates nasopharyngeal cancer cell autophagy, metabolism, and apoptosis in vitro

Wenjuan Li, Xiaoling Li, Wei Wang, Mei Yi, Yanhong Zhou, Pan Zheng, Wei Xiong, Jianbo Yang, Shuping Peng, James B. McCarthy, Bo Xiang, Guiyuan Li

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Autophagy is a cellular survival mechanism that involves the catabolic degradation of damaged proteins and organelles during stress. It is particularly required for tumor cell survival during starvation and tumorigenesis. NOR1 is a putative tumor suppressor gene. This study investigated in vitro the effects of NOR1 on the regulation of nasopharyngeal carcinoma autophagy, metabolism, and apoptosis. The data showed that acute oxidative stress induced the expression of NOR1 in normal human cells and tumor cells. Restoration of NOR1 expression downregulated basal autophagy, assessed by autophagy marker LC3 conversion and transmission electron microscopy. In NOR1-expressing tumor cells, reduced autophagy inhibited mitochondrial respiration and energy metabolism. Restoration of NOR1 expression in nasopharyngeal carcinoma cells enhanced apoptosis after induction of oxidative stress. NOR1 expression upregulated Bax expression, Bax translocation to the mitochondria, Smac/DIABLO release from the mitochondria, and activation of caspase-9, and -3, and PARP. In contrast, knockdown of NOR1 expression using NOR1 RNAi resulted in an increase in autophagy and attenuated hydrogen peroxide-induced cell death in HeLa cells. In addition, expression of NOR1 significantly inhibited cisplatin-induced autophagy, resulting in increased cisplatin cytotoxicity and apoptosis. These data revealed novel aspects of the interplay between autophagy and apoptosis in nasopharyngeal carcinoma cells, which underlies the tumor suppression function of NOR1. This work may provide novel insights to contribute to the development of a combinatorial therapy for nasopharyngeal carcinoma.

Original languageEnglish (US)
Pages (from-to)2016-2026
Number of pages11
JournalInternational Journal of Biochemistry and Cell Biology
Volume45
Issue number9
DOIs
StatePublished - 2013

Bibliographical note

Funding Information:
This study was supported in part by grants from National Natural Science Foundation of China (# 81000883 , # 81102065 , # 81272254 , and # 91229122 ), the National “111” Project (Project #111-2-12), Specialized Research Fund for the Doctoral Program of Higher Education ( 20110162120009 ), The Free Exploration Program of Central South University of China (# 201012200017 and # 2011QNZT138 ), Hunan Provincial Innovation Foundation For Postgraduate (# CX2011B051 ), the Graduate Degree Thesis Innovation Foundation of Central South University of China (# 2010ssxt048 ) and a Scholarship Award for Excellent Doctoral Student from Chinese Ministry of Education (# 106601011 ).

Keywords

  • Apoptosis
  • Autophagy
  • NOR1
  • Oxidative stress
  • Tumor suppressor gene

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