Pamidronate and 1,24(S)-dihydroxyvitamin D2 synergistically inhibit the growth of myeloma, breast and prostate cancer cells.

Bone Care International, 1600Aspen Commons, Middleton, WI 53562, USA. dwigington@bonecare.com

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.

PMID: 16158925 [PubMed - indexed for MEDLINE]