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.

• Authors: D P Wigington, S A Strugnell, J C Knutson
• Journal: Anticancer research (Anticancer Res) 2005 May-Jun Vol. 25 Issue 3B Pg. 1909-17 ISSN: 0250-7005 [Print] Greece
• PMID: 16158925 (Publication Type: Journal Article)

Chemical References

• Diphosphonates
• Ergocalciferols
• 1,24-dihydroxyvitamin D2
• Pamidronate

Topics

• Antineoplastic Combined Chemotherapy Protocols (pharmacology)
• Breast Neoplasms (drug therapy, pathology)
• Cell Growth Processes (drug effects)
• Cell Line, Tumor
• Diphosphonates (administration & dosage, pharmacology)
• Dose-Response Relationship, Drug
• Drug Synergism
• Ergocalciferols (administration & dosage, pharmacology)
• Humans
• Male
• Multiple Myeloma (drug therapy, pathology)
• Pamidronate
• Prostatic Neoplasms (drug therapy, pathology)