cis-Diamminedichloroplatinum(II) resistant human tumor cell lines are collaterally sensitive to PtCl4(Rh-123)2: evidence for mitochondrial involvement.

Abstract

Three human tumor cell lines made resistant to cis-diamminedichloroplatinum(II) (CDDP), SCC-25/CP, MCF-7/CP, and C13, are more sensitive to rhodamine-123 [tetrachloroplatinum(II)] [(PtCl4(Rh-123)2] than are the corresponding parental cell lines. The CDDP-resistant cells have higher intracellular concentrations of PtCl4(Rh-123)2 for the same exposure than do the parent cells. Each of the CDDP-resistant cell lines has an increased level of cytochrome c oxidase activity compared with the parent cell lines, indicating that the resistant cells have greater mitochondrial mass or activity than the parent cells. In fact, there was a linear correlation between the increase in cytochrome c oxidase activity and the increased sensitivity to PtCl4(Rh-123)2 in the CDDP-resistant lines. Exposure of the cells to each of the mitochondrial effectors, chloramphenicol, FCCP, oligomycin, or antimycin prior to and during exposure to CDDP or PtCl4(Rh-123)2 had variable effects on the cytotoxicity of the platinum complexes in the parental lines. However, there was a consistent decrease in the cytotoxicity of PtCl4(Rh-123)2 in the CDDP-resistant cells in the presence of the mitochondrial effectors such that, in some cases, the CDDP-resistant lines were now less responsive to PtCl4(Rh-123)2 than were the parent cell lines. These studies indicate that mitochondrial alterations may be an important component of CDDP resistance in these cell lines and that PtCl4(Rh-123)2 may represent a prototype platinum complex useful in the treatment of CDDP resistant tumors.

• Authors: G Ara, T Kusumoto, T T Korbut, F Cullere-Luengo, B A Teicher
• Journal: Cancer research (Cancer Res) Vol. 54 Issue 6 Pg. 1497-502 (Mar 15 1994) ISSN: 0008-5472 [Print] United States
• PMID: 8137254 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• Organoplatinum Compounds
• Rhodamines
• tetrachloroplatinate dianion-rhodamine-123 complex
• Cisplatin

Topics

• Adenocarcinoma (drug therapy, metabolism)
• Antineoplastic Agents (pharmacology)
• Breast Neoplasms (drug therapy, metabolism)
• Carcinoma, Squamous Cell (drug therapy, metabolism)
• Cell Survival (drug effects)
• Cisplatin (pharmacology)
• Drug Resistance
• Drug Screening Assays, Antitumor
• Female
• Humans
• Intracellular Fluid (metabolism)
• Kinetics
• Mitochondria (drug effects, physiology)
• Neoplasms, Experimental (drug therapy, metabolism)
• Organoplatinum Compounds (pharmacology)
• Ovarian Neoplasms (drug therapy, metabolism)
• Rhodamines (pharmacology)
• Tumor Cells, Cultured (drug effects)