Cytotoxicity of tetraplatin and cisplatin for human and rodent cell lines cultured as monolayers and multicellular spheroids.
The cytotoxicity of tetraplatin (dl-trans), its d- and l-isomers, and cisplatin for four human tumor cell lines (myeloma 8226, ovarian 2008, A2780, and OVCAR-3), their cisplatin-resistant variants, and three rodent cell lines (V79, EMT6/Ro, and L1210) were compared. Tetraplatin was more, or equally as, potent as cisplatin for the human cell lines and for L1210 but was clearly less potent for V79 and EMT6/Ro. The d-trans tetraplatin was more potent than the l-trans. Cisplatin resistant human tumor cells were less resistant to tetraplatin. On comparing sensitivity of V79 and EMT6/Ro cells in two growth models, we observed that all of the platinum compounds were more cytotoxic to cells in multicellular spheroids than in exponentially growing monolayers. Uptake studies, however, showed that tetraplatin was more cytotoxic to spheroids because spheroids accumulated more drug than monolayers.
Bhuyan
B K
BK
Department of Cancer Research, Upjohn Company, Kalamazoo, MI 49001.
Folz
S J
SJ
DeZwaan
J
J
Northcott
S E
SE
Alberts
D S
DS
Garcia
D
D
Wallace
T L
TL
Li
L H
LH
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002945:Cisplatin / Q000633:toxicity*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007536:Isomerism; D007928:Lethal Dose 50; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy; D051379:Mice; D009101:Multiple Myeloma / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000633:toxicity*; D010051:Ovarian Neoplasms / Q000188:drug therapy; D014407:Tumor Cells, Cultured
D009944:Organoplatinum Compounds; D002945:Cisplatin; C049777:ormaplatin