title: Anti-growth effect of 1,25-dihydroxyvitamin D3-3-bromoacetate alone or in combination with 5-amino-imidazole-4-carboxamide-1-beta-4-ribofuranoside in pancreatic cancer cells.
abstract: 1,25-Dihydroxyvitamin D(3)-3-bromoacetate (1,25(OH)(2)D(3)-3-BE) is a vitamin D receptor-alkylating derivative of 1,25(OH)(2)D(3). The strong dose-dependent antiproliferative and apoptotic effects of this compound in androgen-sensitive and androgen-insensitive prostate cancer cells have been reported. In this communication, it is reported that 1,25(OH)(2)D(3)-3-BE strongly inhibits the growth of several pancreatic cancer cell lines. This effect is further accentuated by combination with 5-amino-imidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR), an activator of AMP-activated protein kinase (AMPK)/acetyl-Co-enzyme A carboxylase (ACC) phosphorylation pathways and an inhibitor of Akt phosphorylation. It was observed that the anti-growth property of 1,25(OH)(2)D(3)-3-BE, either alone or in combination with AICAR resulted in the inhibition of Akt phosphorylation in BxPC-3 cells. In conclusion, 1,25(OH)(2)D(3)-3-BE displays a strong therapeutic potential, alone and in combination with AICAR, in pancreatic cancer.
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Kelly S
authors.initials: KS
authors.lastname: Persons
authors.forename: Vikram J
authors.initials: VJ
authors.lastname: Eddy
authors.forename: Susan
authors.initials: S
authors.lastname: Chadid
authors.forename: Rosangela
authors.initials: R
authors.lastname: Deoliveira
authors.forename: Asish K
authors.initials: AK
authors.lastname: Saha
authors.forename: Rahul
authors.initials: R
authors.lastname: Ray
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000620:Aminoimidazole Carboxamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D002117:Calcitriol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000032:analysis; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012265:Ribonucleotides / Q000008:administration & dosage / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: C104313:1,25-dihydroxyvitamin D3-3-bromoacetate; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D012265:Ribonucleotides; D016159:Tumor Suppressor Protein p53; D000620:Aminoimidazole Carboxamide; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase; C031143:AICA ribonucleotide; D002117:Calcitriol