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.