Anti-growth effect of 1,25-dihydroxyvitamin D₃-3-bromoacetate alone or in combination with 5-amino-imidazole-4-carboxamide-1-β-4- ribofuranoside in pancreatic cancer cells

1,25-Dihydroxyvitamin D₃-3-bromoacetate (1,25(OH) ₂D₃-3-BE) is a vitamin D receptor-alkylating derivative of 1,25(OH)₂D₃. The strong dose-dependent anti-proliferative 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)₂D₃-3-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-β-4-ribofuranoside (AICAR), an activator of AMP-activated protein kinase (AMPK)/acetyl-Co-enzyme A carboxylase (ACC) phosphorylation pathways and an inhibitor of Akt phophorylation. It was observed that the anti-growth property of 1,25(OH)₂D₃-3-BE, either alone or in combination with AICAR resulted in the inhibition of Akt phosphorylation in BxPC-3 cells. In conclusion, 1,25(OH)₂D₃-3-BE displays a strong therapeutic potential, alone and in combination with AICAR, in pancreatic cancer.