Journal article
Inhibition of pyruvate carboxylase by 1α,25-dihydroxyvitamin D promotes oxidative stress in early breast cancer progression
Cancer letters, Vol.411, pp.171-181
12/28/2017
DOI: 10.1016/j.canlet.2017.09.045
PMCID: PMC5763507
PMID: 29024812
Abstract
Maintaining reductive-oxidative (redox) balance is an essential feature in breast cancer cell survival, with cellular metabolism playing an integral role in maintaining redox balance through its supply of reduced NADPH. In the present studies, the effect of 1,25-dihydroxyvitamin D (1,25(OH)2D) on redox balance was investigated in early stages of breast cancer. Treatment with 1,25(OH)2D promoted oxidative stress in MCF10A-ras and MCF10A-ErbB2 breast epithelial cells, as measured by the decreased ratios of NADPH/NADP+ and reduced to oxidized glutathione (GSH/GSSG). The mRNA and protein expression of the enzyme pyruvate carboxylase (PC) was downregulated with 1,25(OH)2D treatment, suggesting a potential mechanism. Genetic depletion of PC in MCF10A-ras cells resulted in a decreased ratio of NADPH/NADP+ and GSH/GSSG, with 1,25(OH)2D treatment having no further effect. Mutation analysis confirmed the presence and functionality of a vitamin D response element in the PC gene promoter region. Collectively, these results provide evidence that 1,25(OH)2D promotes oxidative stress in early breast cancer progression through transcriptional downregulation of PC.
•1,25(OH)2D promotes oxidative stress in transformed breast epithelial cells.•1,25(OH)2D transcriptionally downregulates pyruvate carboxylase (PC).•Genetic depletion of PC promotes oxidative stress.•1,25(OH)2D acts as a prooxidant through downregulating PC expression.
Details
- Title: Subtitle
- Inhibition of pyruvate carboxylase by 1α,25-dihydroxyvitamin D promotes oxidative stress in early breast cancer progression
- Creators
- Tomasz Wilmanski - Purdue University West LafayetteXuanzhu Zhou - Purdue University West LafayetteWei Zheng - Purdue University West LafayetteAparna Shinde - Purdue University West LafayetteShawn S. Donkin - Purdue University West LafayetteMichael Wendt - Purdue University West LafayetteJohn R. Burgess - Purdue University West LafayetteDorothy Teegarden - Purdue University West Lafayette
- Resource Type
- Journal article
- Publication Details
- Cancer letters, Vol.411, pp.171-181
- Publisher
- Elsevier B.V
- DOI
- 10.1016/j.canlet.2017.09.045
- PMID
- 29024812
- PMCID
- PMC5763507
- ISSN
- 0304-3835
- eISSN
- 1872-7980
- Language
- English
- Date published
- 12/28/2017
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984460325202771
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