Cis-retinol dehydrogenase: 9-cis-retinol metabolism and its effect on proliferation of human MCF7 breast cancer cells
Journal Article
·
· Experimental Cell Research
- Department of Pathobiology, University of Washington, Seattle, WA 98195 (United States)
- Department of Medicine and Institute of Human Nutrition, Columbia University, New York, NY 10032 (United States)
- Department of Pathology, University of Washington, Seattle, WA 98195 (United States)
9-Cis-retinoic acid (RA) suppresses cancer cell proliferation via binding and activation of nuclear receptors, retinoid X receptors (RXRs). In vivo, 9-cis-RA is formed through oxidation of 9-cis-retinol by cis-retinol dehydrogenase (cRDH), an enzyme that we characterized previously. Since 9-cis-RA is a potent inhibitor of breast cancer cell proliferation, we hypothesized that overexpression of cRDH in breast cancer cells would result in increased production of 9-cis-RA, which in turn would suppress cell proliferation. To investigate this hypothesis, MCF7 human breast carcinoma cells were transduced with cRDH cDNA (LRDHSN/MCF7), and the growth kinetics and retinoid profiles of cells were examined following treatment with 9-cis-retinol. LRDHSN/MCF7 cells showed a marked reduction in cell numbers (60-80%) upon treatment with 9-cis-retinol compared to vehicle alone. Within 24 h of treatment, approximately 75% of the 9-cis-retinol was taken up and metabolized by LRDHSN/MCF7 cells. Despite the rapid uptake and oxidation of 9-cis-retinol to 9-cis-retinal, 9-cis-RA was not formed in these cells. We detect at least one novel metabolite formed from both 9-cis-retinol and 9-cis-retinal that may play a role in inhibition of MCF7 cell proliferation. Our studies demonstrate that 9-cis-retinol in combination with cRDH inhibits breast cancer cell proliferation by production of retinol metabolites other than RA.
- OSTI ID:
- 20717529
- Journal Information:
- Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 1 Vol. 303; ISSN 0014-4827; ISSN ECREAL
- Country of Publication:
- United States
- Language:
- English
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