Effect of prooxidants on mitochondrail permeability transition and cell death in Ehrlich ascites tumour cells

Abstract

Ca2+ retention in mitochondria, opening of the Cysclosporin A‐ sensitive permeability transition pore and cell death were studied in Ehrlich ascites tumour cells in the presence of different prooxidants. Low concentrations (1‐20 μM) of the prooxidants (menadione, cumenehydroperoxide, t‐butylhydroperoxide) induced pore‐opening in permeabilized cells at threshold Ca2+ load. Incubation of cells with low concentrations of prooxidants was able to induce cell cycle disturbance and cell death. Under the prooxidant effect, mitochondrial membrane potential drop and Ca2+ retention decrease in mitochondria were found to precede death of Ehrlich ascites tumour cells.

Suppression of Mitochondrial Permeability Transition Pore and Induction of Lymphoma P388 Cell Death by Cyclosporin A

“…The CsA-induced formation of ROS can be the initial cause provoking the destruction of the tumour P388 cells by way of the apoptosis mechanism. However, in both cases-the normal cells and the tumour cells-one can conceive that at the nal stages of the apoptosis an irreversible PTP opening is developed, as we showed elsewhere in the prooxidant-induce d death of Ehrlich ascites tumour cells (40). From all our experiments, we conclude that CsA and N -methyl-Val-4-CsA induce tumour cell death as a result of initial PTP closing and increased formation of ROS.…”

Pluronics and MDR Reversal: An Update

“…In mitochondria Pluronic may undergo chemical reaction and provide peroxides to respiratory chain. In other words Pluronic may act as a prooxidant, which were shown to induce apoptosis in cancer cells . Noteworthy, the effects of Pluronic on Pgp activity, ATP levels, and cytotoxicity are reversible.…”

Mitochondrial Uptake of Ca2+ and Other Bivalent Cations

“…Thus RLM respiring on succinate were found to be able to temporarily lower the steady state of external [Ca 2+ ] after addition of an external pulse of Ca 2+ [64]. The rate of efflux was not changed by inhibition of the MCU by ruthenium red, or by following the efflux rate after preloading the mitochondrial Ca 2+ with 45 Ca. Nor was it changed by cyclosporine A or diltiazem to inhibit Ca 2+ efflux through the permeability transition pore or Ca 2+ exchange on the Ca 2+ / nNa + antiporter by which accumulated Ca 2+ may be returned to the cytosol [65].…”

“…The former mentions mitochondrial Ca 2+ handling as one of the important factors, the other describes the important apoptosis-inducing factor (AIF). An important factor in cell death is the Ca 2+ induced increased formation of reactive oxygen species (ROS) in mitochondria, leading to opening of the permeability transition pore, cytochrome c release and apoptosis [44][45][46][47].…”