Cisplatinum is currently used as a front line agent in many important
tumors, but its dose-limiting nephrotoxicity prevents potential efficacy. There is therefore great interest in developing new
platinum agents that have less toxicity. We have synthesized new
platinum analogues containing
DACH as a carrier
ligand and
DPPE as a leaving group. Previously we showed that these new
platinum complexes have much less nephrotoxicity than cisplatinum. In the present study, the efficacy of one new
platinum complex was evaluated with human patient
bladder tumor specimens in three-dimensional histoculture as well as with monolayer cultures of
cancer cell lines. The efficacy end points used were
glucose consumption and
thymidine incorporation on the histocultured specimens and MTT reduction on monolayer cell cultures. Our results showed that the new
platinum complex was more effective at high concentration (10(-3) M) but less effective at low concentration (10(-4) M) compared to cisplatinum on histocultured
bladder tumor specimens. The compound demonstrated higher efficacy than cisplatinum on P-388, and L-1210 leukemic cell lines. The new analog demonstrated similar efficacy to cisplatinum on the MKN-45 human
stomach cancer cell line. The PC-14 human
lung cancer cell line, MH1C1 rat
hepatoma cell line, NIH-OV3, SKOV-3
ovarian cancer cell lines were as sensitive to the new analog as to cisplatinum at high concentrations of the new
platinum analogue. The cisplatinum-resistant M-14
melanoma cell line was not sensitive to either the new analog or cisplatinum. Based on these results, this novel
platinum compound appears to be a valuable lead compound with high efficacy and low nephrotoxicity.