7-N-(2-([2-(gamma-L-glutamylamino)-ethyl]-dithio)-ethyl)-mitomycin C (KW-2149) is more active than mitomycin C on chemonaive and drug-resistant urothelial carcinoma cells.
This in vitro study aimed to investigate the cytotoxic activity of 7-N-(2-([2-(gamma-L-glutamylamino)ethyl]dithio)ethyl)-mitomycin C (KW-2149) versus mitomycin C (MMC) against cell lines from human transitional cell carcinoma (TCC). Direct cytotoxicity of the two drugs was measured employing a colorimetric cytotoxicity assay on chemonaive and chemoresistant cancer cell populations. The results revealed that all cell lines (n = 19) were significantly more inhibited by treatment (2 h, 96 h) with KW-2149 than by MMC (P < 0.03-0.001). pH 6.0 decreased the stronger activity of KW-2149 (P < 0.013-0.004). Creatinine > or =10 mmol/l and nitrosourea > or =100 mg/l also inhibited the activity of KW-2149 significantly. Tumor cells with relative drug-resistance against MMC (RT112-MMC: 55-fold) exerted minor cross-resistance to KW-2149 (fourfold). In conclusion, the present in vitro data suggest KW-2149 to be a superior drug for intravesical therapy of patients with primary or recurrent superficial bladder carcinoma. Since pH and concentrations of creatinine and nitrosourea influence the activity of KW-2149, patients are supposed to profit from neutralizing the urinary pH and enhanced diureses.
Rohde
D
D
Department of Urology, Medical Faculty, University of Aachen, Germany.
Raffenberg
G
G
Kaviani
S
S
Wolff
J
J
Jakse
G
G
D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy*; D004347:Drug Interactions; D019008:Drug Resistance, Neoplasm; D006801:Humans; D006863:Hydrogen-Ion Concentration; D016685:Mitomycin / Q000008:administration & dosage / Q000494:pharmacology*; D008937:Mitomycins; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D008937:Mitomycins; C057625:KW 2149; D016685:Mitomycin