کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1992614 1541078 2007 4 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Evaluation of C-2-substituted 19-nor-1α,25-dihydroxyvitamin D3 analogs as therapeutic agents for prostate cancer
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Evaluation of C-2-substituted 19-nor-1α,25-dihydroxyvitamin D3 analogs as therapeutic agents for prostate cancer
چکیده انگلیسی

1α,25-Dihydroxyvitamin D3 (1α,25(OH)2D3) is known to inhibit the proliferation and invasiveness of prostate cancer cells. However, 1α,25(OH)2D3 can cause hypercalcemia and is not suitable as a therapeutic agent. 19-Nor-vitamin D derivatives are known to be less calcemic when administered systemically. In order to develop more potent anti-cancer agents with less calcemic side effect, we therefore utilized 3H-thymidine incorporation as an index for cell proliferation and examined the antiproliferative activities of nine C-2-substituted 19-nor-1α,25(OH)2D3 analogs in the immortalized PZ-HPV-7 normal prostate cell line. Among the nine analogs we observed that the substitution with 2α- or 2β-hydroxypropyl group produced two analogs having antiproliferative potency that is approximately 500- to 1000-fold higher than 1α,25(OH)2D3. The 3H-thymidine incorporation data were supported by the cell counting data after cells were treated with 1α,25(OH)2D3, 19-nor-2α-(3-hydroxypropyl)-1α,25(OH)2D3 or 19-nor-2β-(3-hydroxypropyl)-1α,25(OH)2D3 for 7 days. 19-Nor-2α-(3-hydroxypropyl)-1α,25(OH)2D3 and 19-nor-2β-(3-hydroxypropyl)-1α,25(OH)2D3 were also shown to be about 10-fold more active than 1α,25(OH)2D3 in cell invasion studies using prostate cancer cells. In conclusion, a substitution at the C-2 position of 19-nor-1α,25(OH)2D3 molecule with a hydroxypropyl group greatly increased the antiproliferative and anti-invasion potencies. Thus, these two analogs could be developed to be effective therapeutic agents for treating early and late stages of prostate cancer.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The Journal of Steroid Biochemistry and Molecular Biology - Volume 103, Issues 3–5, March 2007, Pages 717–720
نویسندگان
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