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


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.


CONCLUSIONS
Combined dosing of pamidronate and 1,24(OH)2D2 may have therapeutic value for the treatment of multiple myeloma, prostate and breast cancers.
Wigington
D P
DP
Bone Care International, 1600Aspen Commons, Middleton, WI 53562, USA. dwigington@bonecare.com
Strugnell
S A
SA
Knutson
J C
JC
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D004164:Diphosphonates / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004872:Ergocalciferols / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D000077268:Pamidronate; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology
D004164:Diphosphonates; D004872:Ergocalciferols; C063087:1,24-dihydroxyvitamin D2; D000077268:Pamidronate