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https://hdl.handle.net/2440/41934
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Type: | Journal article |
Title: | Antineoplastic agents target the 25-hydroxyvitamin D-3 24-hydroxylase messenger RNA for degradation: implications in anticancer activity |
Author: | Tan, J. Dwivedi, P. Anderson, P. Nutchey, B. O'Loughlin, P. Morris, H. May, B. Ferrante, A. Hii, C. |
Citation: | Molecular Cancer Therapeutics, 2007; 6(12 Part 1):3131-3138 |
Publisher: | Amer Assoc Cancer Research |
Issue Date: | 2007 |
ISSN: | 1535-7163 1538-8514 |
Statement of Responsibility: | Joseph Tan, Prem P. Dwivedi, Paul Anderson, Barbara K. Nutchey, Peter O'Loughlin, Howard A. Morris, Brian K. May, Antonio Ferrante and Charles S. Hii |
Abstract: | Calcitriol or 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] has antitumor activity and hence its levels in patients may play an important role in disease outcome. Here, we report that the antineoplastic agents, daunorubicin hydrochloride, etoposide, and vincristine sulfate inhibited the ability of 1,25(OH)(2)D(3) to cause the accumulation of mRNA for kidney 25-hydroxyvitamin D(3) 24-hydroxylase (CYP24), an enzyme which catabolizes this hormone. This was not due to a drug-induced cytotoxic effect, reduction in the expression of the vitamin D receptor or inhibition of the vitamin D receptor-mediated activation of the mitogen-activated protein kinases or CYP24 promoter activity. Interestingly, there was selective degradation of CYP24 mRNA in the presence of the drugs. This was accompanied by an enhancement in the levels of 1,25(OH)(2)D(3) in cells incubated with 25-hydroxy vitamin D(3). These data identify a novel mechanism of action of some commonly used antineoplastic agents which by decreasing the stability of CYP24 mRNA would prolong the bioavailability of 1,25(OH)(2)D(3) for anticancer actions. |
Keywords: | COS Cells Cell Line, Tumor Animals Humans Steroid Hydroxylases Mitogen-Activated Protein Kinases RNA, Messenger Antineoplastic Agents Up-Regulation Promoter Regions, Genetic Vitamin D3 24-Hydroxylase Chlorocebus aethiops |
Description: | © 2007 American Association for Cancer Research |
DOI: | 10.1158/1535-7163.MCT-07-0427 |
Published version: | http://dx.doi.org/10.1158/1535-7163.mct-07-0427 |
Appears in Collections: | Aurora harvest Molecular and Biomedical Science publications |
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