1. Antineoplastic agents target the 25-hydroxyvitamin D3 24-hydroxylase messenger RNA for degradation: implications in anticancer activity
- Author
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Joseph Tan, Charles S. T. Hii, Antonio Ferrante, Paul H. Anderson, Brian K. May, Peter D. O’Loughlin, Barbara K. Nutchey, Howard A. Morris, Prem P. Dwivedi, Tang, J, Dwivedi, Prem, Anderson, Paul, Nutchey, Barbara, O'Loughlin, Peter, Morris, Howard Arthur, May, Brian, Ferrante, Antonio, and Hii, Charles
- Subjects
Cancer Research ,Vincristine Sulfate ,Calcitriol ,Oncology and Carcinogenesis ,Antineoplastic Agents ,Vitamin D3 24-Hydroxylase ,Biology ,Pharmacology ,Calcitriol receptor ,Cell Line, Tumor ,Chlorocebus aethiops ,medicine ,Vitamin D and neurology ,Animals ,Humans ,RNA, Messenger ,Promoter Regions, Genetic ,Daunorubicin Hydrochloride ,Kinase ,Up-Regulation ,Oncology ,Mechanism of action ,COS Cells ,Steroid Hydroxylases ,Mitogen-Activated Protein Kinases ,medicine.symptom ,medicine.drug - Abstract
Calcitriol or 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] 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)2D3 to cause the accumulation of mRNA for kidney 25-hydroxyvitamin D3 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)2D3 in cells incubated with 25-hydroxy vitamin D3. 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)2D3 for anticancer actions. [Mol Cancer Ther 2007;6(12):3131–8]
- Published
- 2007