Pamidronate and 1,24(S)-Dihydroxyvitamin D₂ Synergistically Inhibit the Growth of Myeloma, Breast and Prostate Cancer Cells

Abstract

Background: Bisphosphonates have proven to be effective in the management of multiple myeloma and bone metastases secondary to breast and prostate carcinoma. Vitamin D compounds are important modulators of cellular proliferation and differentiation. 1,24(S)-dihydroxyvitamin D₂ [1,24(OH)₂D₂] is a naturally occurring active vitamin D compound with high antiproliferative activity and low calcemic response. Materials and Methods: We examined the antiproliferative effects of 1,24(OH)₂D₂ in combination with the bisphosphonate pamidronate on multiple myeloma (H929), prostate (LNCaP) and breast (MCF-7) cancer cell lines. Drug-drug interactions were analyzed using the median-effect/isobologram method to characterize the interactions as synergistic, additive, or antagonistic. Results: Pamidronate and 1,24(OH)₂D₂ were found independently to inhibit cancer cell growth in a dose-dependent manner. Combinations of these compounds produced marked synergistic growth-inhibitory effects at several clinically relevant concentrations. Conclusion: Combined dosing of pamidronate and 1,24(OH)₂D₂ may have therapeutic value for the treatment of multiple myeloma, prostate and breast cancers.