Please use this identifier to cite or link to this item: 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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