RRC ID |
58107
|
著者 |
Fujitani N, Yoneda A, Takahashi M, Takasawa A, Aoyama T, Miyazaki T.
|
タイトル |
Silencing of Glutathione S-Transferase Pi Inhibits Cancer Cell Growth via Oxidative Stress Induced by Mitochondria Dysfunction.
|
ジャーナル |
Sci Rep
|
Abstract |
Antitumor drug development based on the concept of intervening in the antioxidant system of cancer cells has been gaining increased interest. In this study, we propose a promising strategy for cancer treatment using modulation of oxidative stress by suppression of glutathione S-transferases (GSTs), a typical antioxidant enzyme. siRNA which can be applied to the development of nucleic acid drugs, enabling them to eliminate unwanted side effects, increase specificity, and avoid the problem of drug resistance, was employed for GSTP-silencing at the transcriptional level. The silencing of the pi class of GST (GSTP) that displayed the most characteristic expression profile in 13 kinds of cancer cell lines has shown significant impairment in the growth of cancer cells due to oxidative stress caused by excess ROS accumulation. Comparative proteomics between normal cells and GSTP-silenced pancreatic cancer cell PANC-1 suggested that GSTP-silencing facilitated the mitochondrial dysfunction. These findings show promise for the development of strategies toward cancer therapy based on the mechanism that allows genetic silencing of GSTP to promote oxidative stress through mitochondria dysfunction.
|
巻・号 |
9(1)
|
ページ |
14764
|
公開日 |
2019-10-14
|
DOI |
10.1038/s41598-019-51462-9
|
PII |
10.1038/s41598-019-51462-9
|
PMID |
31611630
|
PMC |
PMC6791853
|
MeSH |
Cell Line, Tumor
Cell Proliferation
Glutathione S-Transferase pi / genetics*
Glutathione S-Transferase pi / metabolism
Humans
Mitochondria / genetics*
Mitochondria / metabolism
Mitochondria / pathology
Oxidative Stress*
Pancreatic Neoplasms / genetics*
Pancreatic Neoplasms / metabolism
Pancreatic Neoplasms / pathology
Pancreatic Neoplasms / therapy
RNA Interference
RNA, Small Interfering / genetics
RNAi Therapeutics
|
IF |
3.998
|
引用数 |
4
|
リソース情報 |
ヒト・動物細胞 |
MCF7(RCB1904)
PANC-1(RCB2095)
MIA Paca2(RCB2094)
HCT116(RCB2979)
Hep G2
HeLa |