AI Article Synopsis

  • Glutathione (GSH) reduces the effectiveness of cisplatin, a chemotherapy drug, in human leukaemia and ovarian cancer cells, but the addition of a copper complex [Cu(phen)(OH)](ClO) restores sensitivity to cisplatin.
  • The combination of the copper complex, cisplatin, and GSH results in a stronger toxic effect on leukaemia cells compared to healthy lymphocytes, suggesting that cancer cells are more vulnerable to this treatment.
  • Treatment with the copper complex and cisplatin triggers early and late apoptotic processes in cancer cells, indicating a strong interaction between these drugs in inducing programmed cell death without harming the cell membrane.

Article Abstract

The antagonistic effect of glutathione (GSH) against the cytotoxicity of cisplatin was observed in both wild type and cisplatin-resistant human leukaemia and ovarian carcinoma cell lines. The simultaneous presence of the cytotoxic copper complex [Cu(phen)(OH)](ClO) (C0) restored the sensitivity of the cells to cisplatin, and, at selected concentrations, led to strong synergistic effects. The C0-cisplatin-glutathione system showed a synergistic toxic effect even in the presence of 1000 μM GSH. The three-drug cocktail exerted a higher potency against leukemic cells than against freshly isolated lymphocytes from healthy donors. Compared to actively proliferating normal lymphocytes, leukaemia cells were much more susceptible to the cytocide effect of the three-drug combination and underwent the dying process(es) much faster. When the ovarian carcinoma cells were treated with cisplatin, alone or in combination with C0, late apoptotic effects were mainly observed, suggesting that DNA interactions with the C0-cisplatin complex trigger a process of programmed cell death. In contrast, the ternary combination induced apoptotic effects similar to that shown by C0 in single treatment, that is, early apoptosis. One possible explanation is that C0 and cisplatin compete for GSH-binding in the culture medium. GSH in combination with C0 and cisplatin caused a significant induction of the apoptotic process(es), through a pathway which does not compromise the integrity of the plasma membrane of cells.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9060805PMC
http://dx.doi.org/10.1039/c8ra09652jDOI Listing

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