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Silencing of Glutathione S-Transferase Pi Inhibits Cancer Cell Growth via Oxidative Stress Induced by Mitochondria Dysfunction

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Title: Silencing of Glutathione S-Transferase Pi Inhibits Cancer Cell Growth via Oxidative Stress Induced by Mitochondria Dysfunction
Authors: Fujitani, Naoki Browse this author →KAKEN DB
Yoneda, Akihiro Browse this author →KAKEN DB
Takahashi, Motoko Browse this author →KAKEN DB
Takasawa, Akira Browse this author →KAKEN DB
Aoyama, Tomoyuki Browse this author →KAKEN DB
Miyazaki, Tadaaki Browse this author →KAKEN DB
Issue Date: 14-Oct-2019
Publisher: Nature Publishing Group
Journal Title: Scientific reports
Volume: 9
Start Page: 14764
Publisher DOI: 10.1038/s41598-019-51462-9
PMID: 31611630
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 mitochondria! 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.
Type: article
Appears in Collections:フード&メディカル イノベーション推進本部 (Center for Food & Medical Innovation) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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