Combination Study of 1,24(S)-Dihydroxyvitamin D₂ and Chemotherapeutic Agents on Human Breast and Prostate Cancer Cell Lines

Abstract

Background: Vitamin D compounds are important modulators of cellular proliferation and differentiation, with potential utility as anticancer drugs. 1,24(S)-Dihydroxyvitamin D₂ [1,24(OH)₂D₂] is a naturally occurring active vitamin D compound with low calcemic activity. Materials and Methods: We evaluated the growth inhibitory effects of 1,24(OH)₂D₂ on LNCaP prostate cancer and MCF-7 breast cancer cells. 1,24(OH)₂D₂ was evaluated alone and in paired combination with nine chemotherapeutic agents. Drug interactions were analyzed using the median-effect/isobologram method. Combination index values were used to characterize the interactions as synergistic, additive, or antagonistic. Results: In MCF-7 cells, 1,24(OH)₂D₂ produced synergistic effects with doxorubicin and cisplatin and additive effects with busulfan, etoposide, tamoxifen, 5-fluorouracil and carboplatin. In LNCaP cells, 1,24(OH)₂D₂ produced a synergistic effect with carboplatin and additive effects with doxorubicin, busulfan, paclitaxel and etoposide. Conclusion: We conclude that 1,24(OH)₂D₂ may have therapeutic value in the treatment of prostate and breast cancers, alone or in combination with chemotherapeutic agents.