Inhibiting 6-phosphogluconate dehydrogenase enhances chemotherapy efficacy in cervical cancer via AMPK-independent inhibition of RhoA and Rac1

Guo, Hongyan; Xiang, Zhao-Yan; Zhang, Y.; Sun, Dao Heng

doi:10.1007/s12094-018-1937-x

Cited by 26 publications

(27 citation statements)

References 25 publications

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“…Like G6PDH, 6PGD was reported to help in sensitizing cisplatin-resistant cells in both ovarian and lung cancer. In addition, 6PGD expression was shown to be linked with poor prognoses in breast cancer patients; thus, its inhibition was suggested to improve breast cancer outcomes [ 49 ]. Therefore, 6PGD overexpression is a successful adaptive (evolutionary) strategy to confer cancer cell survival.…”

Section: Oxidative Phasementioning

confidence: 99%

“…Therefore, 6PGD overexpression is a successful adaptive (evolutionary) strategy to confer cancer cell survival. Therefore, it will not be surprising if there is extensive research on 6PGD as a potential target in cancer management [ 49 ]. Parietin (Physcione) is an anti-infectious agent [ 50 ] and a 6PGD inhibitor [ 45 , 51 , 52 ].…”

Section: Oxidative Phasementioning

confidence: 99%

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The Pentose Phosphate Pathway Dynamics in Cancer and Its Dependency on Intracellular pH

et al. 2020

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The Pentose Phosphate Pathway (PPP) is one of the key metabolic pathways occurring in living cells to produce energy and maintain cellular homeostasis. Cancer cells have higher cytoplasmic utilization of glucose (glycolysis), even in the presence of oxygen; this is known as the “Warburg Effect”. However, cytoplasmic glucose utilization can also occur in cancer through the PPP. This pathway contributes to cancer cells by operating in many different ways: (i) as a defense mechanism via the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) to prevent apoptosis, (ii) as a provision for the maintenance of energy by intermediate glycolysis, (iii) by increasing genomic material to the cellular pool of nucleic acid bases, (iv) by promoting survival through increasing glycolysis, and so increasing acid production, and (v) by inducing cellular proliferation by the synthesis of nucleic acid, fatty acid, and amino acid. Each step of the PPP can be upregulated in some types of cancer but not in others. An interesting aspect of this metabolic pathway is the shared regulation of the glycolytic and PPP pathways by intracellular pH (pHi). Indeed, as with glycolysis, the optimum activity of the enzymes driving the PPP occurs at an alkaline pHi, which is compatible with the cytoplasmic pH of cancer cells. Here, we outline each step of the PPP and discuss its possible correlation with cancer.

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Section: Oxidative Phasementioning

confidence: 99%

Section: Oxidative Phasementioning

confidence: 99%

The Pentose Phosphate Pathway Dynamics in Cancer and Its Dependency on Intracellular pH

et al. 2020

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“…Moreover, it has been reported that SRXN1 promotes cell invasion, migration in cervical cancer via activating the Wnt/β-catenin signaling pathway, and could be a promising tool for the development of better therapeutic strategies for cancer prevention and treatment [45]. Recent work suggested that 6phosphogluconate dehydrogenase (6PGD), the key enzyme of oxidative pentose phosphate pathway (PPP), could act as a potential therapeutic target to enhance chemosensitivity in cervical cancer [46]. In addition,…”

Section: Agingmentioning

confidence: 99%

Integrated data analysis reveals significant associations of KEAP1 mutations with DNA methylation alterations in lung adenocarcinomas

Elshaer

El-Manawy

Hammad

et al. 2020

Aging

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INTRODUCTION Lung cancer is the leading cause of cancer deaths worldwide. Human lung cancers are classified into two major histologic types, small-cell lung cancer and nonsmall-cell lung cancer (NSCLC), the latter comprising several subtypes. Previously, lung squamous cell carcinoma was the predominant form of NSCLC, but in the last few decades it has been replaced by lung adenocarcinoma (LUAD). Moreover, LUAD is the most common type of lung cancer in women, non-smokers, and young people [1]. Epigenetic changes in tumor tissue are involved in the pathogenesis of cancer. DNA methylation is a wellstudied epigenetic alteration in cancer, owing in part to www.aging-us.com

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“…Mounting studies showed that the expression of 6-phosphogluconate dehydrogenase (6PGD) was upregulated in many solid cancers, including colorectal cancers, 1 cervical intraepithelial neoplasia, 2 , 3 liver cancer, 4 cervical cancer, 5 anaplastic thyroid carcinoma (ATC), 6 breast cancer, 7 ovarian cancer and lung cancer. 8 Sukhatme reported that knockdown of 6PGD in lung cancer H1975 cells inhibits cell proliferation in vitro and tumor growth in vivo.…”

Section: Introductionmentioning

confidence: 99%

“…4 Guo et al reported that the inhibition of 6PGD by Physcion enhances chemosensitivity in cervical cancer. 5 Ma et al study demonstrated that inhibiting 6PGD reverses doxorubicin resistance in anaplastic thyroid cancer. 6 Yang et al study suggested that the inhibition of 6PGD by Physcion augments chemotherapy efficacy in breast cancer.…”

Section: Introductionmentioning

confidence: 99%

<p>Discovery of Ebselen as an Inhibitor of 6PGD for Suppressing Tumor Growth</p>

Sun

et al. 2020

CMAR

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Introduction The 6-phosphogluconate dehydrogenase (6PGD) was upregulated in many solid cancers and plays an important role in tumorigenesis. In the present study, we want to discover an old drug as an inhibitor of 6PGD for suppressing tumor growth. Methods We determined the expression of 6PGD in cancer tissues using Gene Expression Omnibus (GEO) profiles and explored the importance of 6PGD expression in cancer progression by using Kaplan–Meier Plotter. We identified Ebselen as a 6PGD inhibitor by using 6PGD in vitro enzyme activity assay. Cell viability, cell proliferation, tumor growth and cell metabolism assay were used to explore the role of 6PGD and its inhibitor in cancer cells. Results We found that the expression of 6PGD was upregulated in different cancer tissues and it can promote tumorigenesis. Here, we analyzed our 6PGD inhibitor screening data again and found an old drug Ebselen, which blocks cancer cell proliferation and tumor growth by inhibiting 6PGD enzyme activity, while knocking down 6PGD would partially abolish the inhibition of Ebselen on cell proliferation and cell metabolism. Conclusion Our results suggested that the conventional drug Ebselen could serve as a novel inhibitor of 6PGD for suppressing cancer growth by inhibiting 6PGD enzyme activity.

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Inhibiting 6-phosphogluconate dehydrogenase enhances chemotherapy efficacy in cervical cancer via AMPK-independent inhibition of RhoA and Rac1

Abstract: Our work is the first to demonstrate the aberrant expression of 6PGD and its predominant roles in cervical cancer cell growth and migration, via a AMPK-dependent activation. Our findings suggest 6PGD as a potential therapeutic target to enhance chemosensitivity in cervical cancer.

Cited by 26 publications

References 25 publications

The Pentose Phosphate Pathway Dynamics in Cancer and Its Dependency on Intracellular pH

The Pentose Phosphate Pathway Dynamics in Cancer and Its Dependency on Intracellular pH

Integrated data analysis reveals significant associations of KEAP1 mutations with DNA methylation alterations in lung adenocarcinomas

<p>Discovery of Ebselen as an Inhibitor of 6PGD for Suppressing Tumor Growth</p>

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