1 alpha,25(OH)2D3 exerts cytostatic effects on murine osteosarcoma cells and enhances the cytocidal effects of anticancer drugs.
The effects of 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25-(OH)2D3), 1 alpha-hydroxyvitamin D3 (1 alpha(OH)D3), and dexamethasone on colony formation of Dunn osteosarcoma cells (TA 102 cells) were investigated. Concentrations of 1 alpha,25(OH)2D3, 1 alpha(OH)D3, and dexamethasone at which they exerted 50% reduction of the total area of TA 102 colony formation were 9 X 10(-9) M, 9 X 10(-8) M, and 5 X 10(-6) M, respectively. Effects of anticancer drugs on TA 102 cells were also investigated and concentrations needed for 50% growth inhibition (50% inhibitory concentration values) of cis-platinum, mitomycin C (MMC), methotrexate (MTX), and Adriamycin (ADR) against TA 102 cells were calculated to be 0.07 microgram/ml, 0.0008 microgram/ml, 0.0008 microgram/ml, and 0.0005 microgram/ml, respectively. The simultaneous treatment of TA 102 cells with 10(-8) M of 1 alpha,25(OH)2D3 and anticancer drugs significantly enhanced the respective inhibitory effects on colony formation. In this treatment, the IC50 value of MMC was calculated to be 6.4 X 10(-6) micrograms/ml, which was 1/160 of the expected IC50 value of MMC (8 X 10(-4) micrograms/ml). Similar synergistic effects were observed when the cells were treated with 1 alpha,25(OH)2D3 and low concentrations of cis-platinum, MTX, or ADR.
Tanaka
H
H
Department of Orthopaedic Surgery, Kyoto University, Japan.
Yamamuro
T
T
Kotoura
Y
Y
Matsumoto
M
M
Tanaká
C
C
Suzuki
S
S
Tsuzi
T
T
Miki
T
T
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002478:Cells, Cultured; D006224:Cricetinae; D004100:Dihydroxycholecalciferols / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D051379:Mice; D012516:Osteosarcoma / Q000188:drug therapy*; D051381:Rats; D014407:Tumor Cells, Cultured
D004100:Dihydroxycholecalciferols; C023850:1 alpha,24-dihydroxyvitamin D3