Oxidative stress, disturbance of energy balance, and death of ascites tumour cells under menadione (vitamin K3) action.

Resting ascites tumour cells (Ehrlich and EL-4 thymoma) treated with menadione (50 microM) died (up to 80% cell death over 2 h) without dividing (i.e. interphase). Glucose (25 mM) added to the cell suspensions partially protected these cells from menadione action. During incubation of the cells with menadione, the rates of free oxidation and lipid peroxidation were elevated, cellular ATP and nonprotein SH-group levels were much decreased, and [Ca2+]i was moderately increased. From a comparison of these effects and cell survival rates with those seen with rotenone, KCN (both inhibitors of oxidative phosphorylation), and H2O2 (an inducer of oxidative stress), it is concluded that ATP depletion is the main factor leading to the death of cells treated with menadione. The level of cellular ATP dropped to less than 10% of its initial value after 1 h incubation with menadione and may have resulted in irreversible damage to cytoskeletal structures, bleb formation, and changes in plasma membrane permeability that are incompatible with cell viability.