Methionine and cystine double deprivation stress suppresses glioma proliferation via inducing ROS/autophagy

Huailei Liu; Weiguang Zhang; Kaikai Wang; Xiaoxiong Wang; Fei Yin; Chenguang Li; Chunlei Wang; Boxian Zhao; Chen Zhong; Jiakang Zhang; Fei Peng; Yunke Bi; Chen Shen; Xu Hou; Daming Zhang; Yaohua Liu; Jing Ai; Shiguang Zhao

doi:10.1016/j.toxlet.2014.11.011

Methionine and cystine double deprivation stress suppresses glioma proliferation via inducing ROS/autophagy

Toxicol Lett. 2015 Jan 22;232(2):349-55. doi: 10.1016/j.toxlet.2014.11.011. Epub 2014 Nov 13.

Authors

Huailei Liu¹, Weiguang Zhang², Kaikai Wang², Xiaoxiong Wang², Fei Yin², Chenguang Li², Chunlei Wang², Boxian Zhao², Chen Zhong², Jiakang Zhang², Fei Peng², Yunke Bi², Chen Shen², Xu Hou², Daming Zhang², Yaohua Liu², Jing Ai³, Shiguang Zhao⁴

Affiliations

¹ Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Nangang District, Harbin, Heilongjiang Province, 150001, People's Republic of China; Institute of Brain Science, Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China; Department of Pharmacology (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China), Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
² Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Nangang District, Harbin, Heilongjiang Province, 150001, People's Republic of China; Institute of Brain Science, Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
³ Department of Pharmacology (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China), Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
⁴ Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Nangang District, Harbin, Heilongjiang Province, 150001, People's Republic of China; Institute of Brain Science, Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China. Electronic address: guangsz@hotmail.com.

PMID: 25448282
DOI: 10.1016/j.toxlet.2014.11.011

Abstract

Cancer cells are highly dependent on methionine and cystine (Met-Cys) for survival and proliferation. However, the molecular mechanism is not fully clear. The present study is to investigate the effects of Met-Cys deprivation on glioma cells proliferation. The results showed that Met-Cys double deprivation had synergistic action on elevating ROS level, decreased GSH level and inhibition of glioma cell proliferation. Moreover, both of them deprivation triggered autophagy of glioma cells both in vitro and in vivo. Importantly, Met-Cys double restriction diet inhibited growth of glioma. These results provided a new regulation mechanism of Met-Cys metabolism on affecting glioma cell proliferation, suggesting that targeting Met-Cys metabolism may be a potential strategy for glioma therapy.

Keywords: Autophagy; Cystine/cysteine; Glioma; Methionine; ROS.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Autophagy / drug effects*
Brain Neoplasms / pathology*
Cell Proliferation
Cystine / deficiency*
Glioma / pathology*
Methionine / deficiency*
Mice
Mice, Inbred BALB C
Mice, Nude
Reactive Oxygen Species / metabolism*

Substances

Reactive Oxygen Species
Cystine
Methionine