Modulation of the in vitro cytotoxicity of seven anticancer drugs by protein synthesis inhibition using sparsomycin

Abstract

Inhibitors of protein synthesis may modify cell response to cytotoxic drugs. The influence of protein synthesis inhibition using sparsomycin (Sm) on the cytotoxicity of seven classical cytotoxic drugs, 5-FU, ARA-C, MTX, doxorubicin, melphalan, bleomycin and vincristine, was studied. Preincubations, simultaneous incubations and postincubations with Sm were investigated in vitro on CHO cells. Preincubation with Sm antagonized the activity of the S phase specific drugs 5-FU, ARA-C, MTX as well as vincristine, while postincubation with Sm enhanced their effect. A similar pattern was observed with doxorubicin. Preincubation with Sm had a potentiated non-S phase specific like bleomycin and cisplatin, but not melphalan. Postincubation with Sm had a potentiating effect on bleomycin but had no effect on melphalan. These results indicate a strong, schedule dependent effect of Sm on various drugs and suggest some potentially useful combinations to be tested in vivo.