[Growth inhibitory effect of a new anticancer antibiotics, kazusamycin A, on human transitional cancer cell lines in vitro].
Kazusamycin A (KZMA) is a new anticancer antibiotic, which has been proven to have strong anticancer effect and several characteristic features different from currently available anticancer antibiotics. However, there has as yet been no report which had concerned itself with the effect of KZMA on urological cancer. This study was undertaken to determine the inhibitory effects of KZMA on transitional cancer cells in vitro, the augmentation of the inhibitory effect by combining thermal treatment and the effect of KZMA upon DNA distribution. Human transitional cancer cells, KU-1, and T-24 were used as targets. Fifty % inhibitory concentration of KZMA was determined after these cells were exposed to graded concentrations of KZMA for 2 to 48 hours, and to the concentration of KZMA for 2 hours at the temperature of 42 degrees C. Viable cells were counted by dye exclusion assay (DEA) and by tetrazolium-based colorimetric assay (MTT-assay) exposure. KZMA inhibited the growth of the three transitional cancer cells strongly and this inhibitory effect appeared to be depend upon the exposure time and the concentration of KZMA. IC50s after 2-hour exposure at the temperature of 42 degrees C was shown to be decreased to 23 to 87% of that at the temperature of 37 degrees, indicating an augmentation of the inhibitory effect of KZMA by combining thermal treatment. MGH-U1 was the most sensitive to the combination of KZMA and hyperthermia. The cell cycle analysis showed that KZMA had G2-arresting and M-retarding effects, which were different compared with currently available anticancer antibiotics.(ABSTRACT TRUNCATED AT 250 WORDS)
Sawamura
M
M
Department of Urology, National Defense Medical College.
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002295:Carcinoma, Transitional Cell / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006801:Humans; D006979:Hyperthermia, Induced; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000473:pathology*
D000903:Antibiotics, Antineoplastic; D005231:Fatty Acids, Unsaturated; C042541:kazusamycin A