Combination study of 1,24(S)-dihydroxyvitamin D2 and chemotherapeutic agents on human breast and prostate cancer cell lines.
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.


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.


CONCLUSIONS
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.
Wigington
D P
DP
Bone Care International, 1600Aspen Commons, Middleton, WI 53562, USA. dwigington@bonecare.com
Urben
C M
CM
Strugnell
S A
SA
Knutson
J C
JC
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy*; D002066:Busulfan / Q000008:administration & dosage; D016190:Carboplatin / Q000008:administration & dosage; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D004347:Drug Interactions; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D004872:Ergocalciferols / Q000008:administration & dosage / Q000494:pharmacology*; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D013629:Tamoxifen / Q000008:administration & dosage
D004872:Ergocalciferols; D013629:Tamoxifen; C063087:1,24-dihydroxyvitamin D2; D005047:Etoposide; D004317:Doxorubicin; D016190:Carboplatin; D002066:Busulfan; D002945:Cisplatin; D005472:Fluorouracil