title: 1alpha,25-Dihydroxyvitamin D3-3beta-(2)-bromoacetate, an affinity labeling derivative of 1alpha,25-dihydroxyvitamin D3 displays strong antiproliferative and cytotoxic behavior in prostate cancer cells.
abstract: In this report we describe that 1,25(OH)(2)D(3)-3-BE, a VDR-affinity labeling analog of 1,25(OH)(2)D(3), showed strong and dose-dependent growth-inhibitory effect in several epithelial cells, i.e., keratinocytes (primary cells), MCF-7 breast cancer, PC-3, and LNCaP prostate cancer and PZ-HPV-7 immortalized normal prostate cell-lines. Furthermore, 10(-6) M of 1,25(OH)(2)D(3)-3-BE induced apoptosis specifically in LNCaP and PC-3 cells; and the effect was much less pronounced at lower doses. We also showed that the effect (of 1,25(OH)(2)D(3)-3-BE) was not due to probable degradation (hydrolysis) of 1,25(OH)(2)D(3)-3-BE or random interaction of this molecule with cellular proteins. Tissue- or cell-specific action of 1,25(OH)(2)D(3) and its mimics is not common due to the ubiquitous nature of VDR. Furthermore, variable effects of 1,25(OH)(2)D(3) and its analogs in various cell-lines potentially limits their application as anticancer agents. We showed that 1,25(OH)(2)D(3)-3-BE displayed similar growth-inhibitory and cytotoxic activities towards androgen sensitive LNCaP and androgen-independent PC-3 cell-lines. Therefore, these results raise the possibility that 1,25(OH)(2)D(3)-3-BE or similar VDR-cross linking analogs of 1,25(OH)(2)D(3) might be considered for further development as potential candidates for prostate cancer.
authors.affiliation: Section in Endocrinology, Diabetes and Metabolism, Department of Medicine, Boston University School of Medicine, 85 East Newton Street, Boston, MA 02118, USA.
authors.forename: Narasimha
authors.initials: N
authors.lastname: Swamy
authors.forename: Kelly S
authors.initials: KS
authors.lastname: Persons
authors.forename: Tai C
authors.initials: TC
authors.lastname: Chen
authors.forename: Rahul
authors.initials: R
authors.lastname: Ray
mesh_terms: D000345:Affinity Labels / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects; D008297:Male; D008751:Methylene Blue / Q000737:chemistry; D011467:Prostate / Q000166:cytology / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018167:Receptors, Calcitriol / Q000737:chemistry / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism
chemical_list: C104313:1,25-dihydroxyvitamin D3-3-bromoacetate; D000345:Affinity Labels; D018167:Receptors, Calcitriol; D002117:Calcitriol; D008751:Methylene Blue; D013936:Thymidine