Bleomycin control of transplasma membrane redox activity and proton movement in HeLa cells

Bleomycin, tallysomycin A, tallysomycin S10b and copper-bleomycin have been tested for their capacity to inhibit the transplasma membrane electron transport and associated proton release by HeLa cells. Transplasma membrane redox activity is measured using reduction of external ferricyanide by the cells. At 75 micrograms/ml bleomycin, tallysomycin A and tallysomycin S10b gave a maximum of 65% inhibition of the ferricyanide reduction rate; half-maximum inhibition was observed at 30 micrograms/ml. The copper-bleomycin complex was slightly more effective as an inhibitor with half-maximum inhibition at 20 micrograms/ml. Survival of cells after 1 hr of drug treatment was 50% at 25 micrograms/ml for bleomycin and copper-bleomycin and at 75 micrograms/ml for tallysomycin A. Tallysomycin A and tallysomycin S10b gave 75 to 83% inhibition of ferricyanide-induced proton extrusion, respectively at 50 micrograms/ml, whereas bleomycin and copper-bleomycin appeared to be slightly less effective with 50 to 60% inhibition, respectively, at 50 micrograms/ml. In all aspects studied, which included transplasma membrane ferricyanide reduction, ferricyanide-induced proton release, and cell survival, there were significant effects by these compounds on HeLa cells in the range of 25-50 micrograms/ml.