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 doxonrubicin and cisplatin and additive effects with busulfan, etoposide, tamaxifen, 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.

• Authors: D P Wigington, C M Urben, S A Strugnell, J C Knutson
• Journal: Anticancer research (Anticancer Res) 2004 Sep-Oct Vol. 24 Issue 5A Pg. 2905-12 ISSN: 0250-7005 [Print] Greece
• PMID: 15517895 (Publication Type: Journal Article)

Chemical References

• Ergocalciferols
• Tamoxifen
• 1,24-dihydroxyvitamin D2
• Etoposide
• Doxorubicin
• Carboplatin
• Busulfan
• Cisplatin
• Fluorouracil

Topics

• Antineoplastic Combined Chemotherapy Protocols (pharmacology)
• Breast Neoplasms (drug therapy)
• Busulfan (administration & dosage)
• Carboplatin (administration & dosage)
• Cell Division (drug effects)
• Cell Line, Tumor
• Cisplatin (administration & dosage)
• Dose-Response Relationship, Drug
• Doxorubicin (administration & dosage)
• Drug Interactions
• Drug Screening Assays, Antitumor
• Drug Synergism
• Ergocalciferols (administration & dosage, pharmacology)
• Etoposide (administration & dosage)
• Female
• Fluorouracil (administration & dosage)
• Humans
• Male
• Prostatic Neoplasms (drug therapy)
• Tamoxifen (administration & dosage)