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Cited by 59Cancer, Hypoxia, and MetabolismMetabolism, Diabetes, and CancerCancer, Lipids, and Metabolism

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Inhibiting 6-phosphogluconate dehydrogenase selectively targets breast cancer through AMPK activation

Yang, Xiaoyu, Peng, Xiaochun, Huang, Jiangrong·2018·Clinical and Translational Oncology
DOI 10.1007/s12094-018-1833-4
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Abstract

Purpose 6-phosphogluconate dehydrogenase (6PGD), a key enzyme of the oxidative pentose phosphate pathway, is involved in tumor growth and metabolism. Although high 6PGD activity has been shown to be associated with poor prognosis, its role and therapeutic value in breast cancer remain unknown. Methods The levels and roles of 6PGD were analyzed in breast cancer cells and their normal counterparts. The underlying mechanisms of 6PGD's roles are also analyzed. Results We found that 6PGD is aberrantly activated in breast cancer as shown by its increased transcriptional and translational levels as well as enzyme activity in breast cancer tissues and cell lines compared to normal counterparts. Although similar degree of enzyme activity inhibition was achieved in both breast cancer and normal breast cells, 6PGD inhibition by siRNA-mediated knockdown or pharmacological inhibitor physcion is more effective in inhibiting growth and survival in breast cancer than normal breast cells. Moreover, inhibiting 6PGD significantly sensitizes breast cancer response to chemotherapeutic agents in in vitro cell culture system and in vivo xenograft breast cancer model. We further show that 6PGD inhibition activates AMPK and its downstream substrate ACC1, leading to reduction of ACC1 activity and lipid biosynthesis. AMPK depletion significantly reverses the inhibitory effects of physcion in breast cancer cells, confirming that 6PGD inhibition targets breast cancer cell via AMPK activation. Conclusions…

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Cited by

Metadata

Authors
Yang, X., Peng, X., & Huang, J.
Affiliations
  • Xiang Yang No.1 People's Hospital (CN)
  • Yangtze University (CN)
Corresponding author
Huang, Jiangrong
ORCID
Venue
Clinical and Translational Oncology
Publisher
Springer Science and Business Media LLC
Published
2018-01-16
Volume
20
Issue
9
Pages
1145-1152
ISSN
  • 1699-048X (ISSN-L)
  • 1699-3055
DOI
10.1007/s12094-018-1833-4
OpenAlex
W2783663785
Cited by
59
References
0
Citations by year
2026: 3 · 2025: 1 · 2024: 5 · 2023: 6 · 2022: 10 · 2021: 10 · 2020: 13 · 2019: 7 · 2018: 4
FWCI
2.56
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Clinical & Translational Oncology (publishedVersion)
  • PubMed (publishedVersion)
Funders
Hubei Provincial Health and Family Planning Commission (2016-2017 15)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Keywords
6-phosphogluconate dehydrogenase, breast cancer, AMPK activation, oxidative pentose phosphate pathway, physcion, acetyl-CoA carboxylase 1, lipogenesis, chemosensitization, cancer metabolism, siRNA knockdown, xenograft models
MeSH terms
Animals, Breast Neoplasms, Enzyme Activation, Female, Humans, Phosphogluconate Dehydrogenase, Cell Line, Tumor, Mice, AMP-Activated Protein Kinases

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