Inhibition of Glucose-6-Phosphate Dehydrogenase Reverses Cisplatin Resistance in Lung Cancer Cells via the Redox System
The pentose phosphate pathway (PPP), which branches from glycolysis, is correlated with cancer cell proliferation, survival and senescence. In this study, differences in the metabolic profile of the PPP and the redox status of human lung carcinoma A549 cells and cisplatin-induced multidrug-resistant...
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doaj-89b10eefe9bc4fa99868df33ee50d8562020-11-25T00:31:03ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-01-01910.3389/fphar.2018.00043325058Inhibition of Glucose-6-Phosphate Dehydrogenase Reverses Cisplatin Resistance in Lung Cancer Cells via the Redox SystemWeipeng Hong0Peiheng Cai1Chuncao Xu2Di Cao3Weibang Yu4Zhongxiang Zhao5Min Huang6Jing Jin7School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, ChinaSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, ChinaSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, ChinaSchool of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, ChinaSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, ChinaSchool of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, ChinaSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, ChinaSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, ChinaThe pentose phosphate pathway (PPP), which branches from glycolysis, is correlated with cancer cell proliferation, survival and senescence. In this study, differences in the metabolic profile of the PPP and the redox status of human lung carcinoma A549 cells and cisplatin-induced multidrug-resistant A549/DDP cells were analyzed and evaluated. The results showed that A549/DDP cells exhibited differential PPP-derived metabolic features and redox-related molecules. A549/DDP cells exhibited increased expression and enzymatic activity of PPP enzyme glucose-6-phosphate dehydrogenase (G6PD). Furthermore, as demonstrated by the apoptotic rate, cell viability, and colony formation, inhibition of G6PD by siRNA or an inhibitor sensitized A549/DDP cells to cisplatin. Additionally, inhibition of G6PD restored the cisplatin sensitivity of A549/DDP cells by influencing redox homeostasis. In conclusion, overcoming cisplatin resistance through inhibition of G6PD could improve the understanding of the mechanisms underlying cisplatin-induced resistance in human lung cancer and may provide insights into the therapeutic potential of this treatment to combat resistance.http://journal.frontiersin.org/article/10.3389/fphar.2018.00043/fullpentose phosphate pathwayG6PDcisplatin resistanceA549A549/DDPredox |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Weipeng Hong Peiheng Cai Chuncao Xu Di Cao Weibang Yu Zhongxiang Zhao Min Huang Jing Jin |
spellingShingle |
Weipeng Hong Peiheng Cai Chuncao Xu Di Cao Weibang Yu Zhongxiang Zhao Min Huang Jing Jin Inhibition of Glucose-6-Phosphate Dehydrogenase Reverses Cisplatin Resistance in Lung Cancer Cells via the Redox System Frontiers in Pharmacology pentose phosphate pathway G6PD cisplatin resistance A549 A549/DDP redox |
author_facet |
Weipeng Hong Peiheng Cai Chuncao Xu Di Cao Weibang Yu Zhongxiang Zhao Min Huang Jing Jin |
author_sort |
Weipeng Hong |
title |
Inhibition of Glucose-6-Phosphate Dehydrogenase Reverses Cisplatin Resistance in Lung Cancer Cells via the Redox System |
title_short |
Inhibition of Glucose-6-Phosphate Dehydrogenase Reverses Cisplatin Resistance in Lung Cancer Cells via the Redox System |
title_full |
Inhibition of Glucose-6-Phosphate Dehydrogenase Reverses Cisplatin Resistance in Lung Cancer Cells via the Redox System |
title_fullStr |
Inhibition of Glucose-6-Phosphate Dehydrogenase Reverses Cisplatin Resistance in Lung Cancer Cells via the Redox System |
title_full_unstemmed |
Inhibition of Glucose-6-Phosphate Dehydrogenase Reverses Cisplatin Resistance in Lung Cancer Cells via the Redox System |
title_sort |
inhibition of glucose-6-phosphate dehydrogenase reverses cisplatin resistance in lung cancer cells via the redox system |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2018-01-01 |
description |
The pentose phosphate pathway (PPP), which branches from glycolysis, is correlated with cancer cell proliferation, survival and senescence. In this study, differences in the metabolic profile of the PPP and the redox status of human lung carcinoma A549 cells and cisplatin-induced multidrug-resistant A549/DDP cells were analyzed and evaluated. The results showed that A549/DDP cells exhibited differential PPP-derived metabolic features and redox-related molecules. A549/DDP cells exhibited increased expression and enzymatic activity of PPP enzyme glucose-6-phosphate dehydrogenase (G6PD). Furthermore, as demonstrated by the apoptotic rate, cell viability, and colony formation, inhibition of G6PD by siRNA or an inhibitor sensitized A549/DDP cells to cisplatin. Additionally, inhibition of G6PD restored the cisplatin sensitivity of A549/DDP cells by influencing redox homeostasis. In conclusion, overcoming cisplatin resistance through inhibition of G6PD could improve the understanding of the mechanisms underlying cisplatin-induced resistance in human lung cancer and may provide insights into the therapeutic potential of this treatment to combat resistance. |
topic |
pentose phosphate pathway G6PD cisplatin resistance A549 A549/DDP redox |
url |
http://journal.frontiersin.org/article/10.3389/fphar.2018.00043/full |
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