In vitro antitumor activity of a new platinum complex, DWA2114R against human tumor cell lines.
The in vitro antitumor activities of a new platinum complex, (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato++ +)platinum(II) monohydrate (DWA2114R), against various human tumor lines (23 solid tumor lines and 6 hematopoietic malignant lines) were examined in comparison with those of cis-diammine (1,1-cyclobutanedicarboxylato) platinum(II) (CBDCA) and cis-diamminedichloroplatinum(II) (CDDP). The growth inhibitory activities of the compounds were estimated by MTT assay after the incubation of cells under continuous exposure to the drug. The mean concentrations (microM) of DWA2114R, CBDCA and CDDP needed to inhibit the proliferation of cells by 50% (IC50) were 64.0, 55.1 and 6.8 against solid tumor lines and 8.5, 7.4 and 1.7 against hematopoietic malignant lines, respectively. Comparing the drug sensitivity of the solid tumor lines by type, ovarian cancer was found to be the most susceptible to all three compounds. The susceptibilities of other tumors were in the order prostate, breast and colon cancers for DWA2114R and CBDCA but colon, prostate and breast cancers for CDDP. The correlations of the mean IC50 values for all three combinations of the two compounds were statistically evaluated. A significant correlation was shown between DWA2114R and CBDCA, or CBDCA and CDDP, but not between DWA2114R and CDDP. These results suggest that DWA2114R is almost equivalent in effect to CBDCA which is several times less potent than CDDP, but also that the in vitro cell line subpanel specificity of DWA2114R is in certain respects different from CDDP, in contrast with CBDCA.
Akamatsu
K
K
Laboratory of Cancer and Hematological Disease, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan.
Saito
H
H
Tsunenari
T
T
Matsumoto
T
T
Morikawa
K
K
Koizumi
M
M
Mitsui
H
H
Koizumi
K
K
D000970:Antineoplastic Agents / Q000633:toxicity*; D001943:Breast Neoplasms; D016190:Carboplatin / Q000031:analogs & derivatives* / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002945:Cisplatin / Q000633:toxicity; D003110:Colonic Neoplasms; D004347:Drug Interactions; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007938:Leukemia; D008223:Lymphoma; D008297:Male; D010051:Ovarian Neoplasms; D011471:Prostatic Neoplasms; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; C058816:DWA 2114; D016190:Carboplatin; D002945:Cisplatin