title: 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.
authors: Department of Internal Medicine, St. Radboud University Hospital, Nijmegen, The Netherlands.
authors: Z
authors: Z
authors: Zylicz
authors: H P
authors: HP
authors: Hofs
authors: D J
authors: DJ
authors: Wagener
authors: H
authors: H
authors: Van Rennes
authors: J M
authors: JM
authors: Wessels
authors: L A
authors: LA
authors: van den Broek
authors: H C
authors: HC
authors: Ottenheijm
mesh_terms: D000277:Adjuvants, Pharmaceutic / Q000494:pharmacology; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001761:Bleomycin / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D002945:Cisplatin / Q000494:pharmacology; D003561:Cytarabine / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D005472:Fluorouracil / Q000494:pharmacology; D008558:Melphalan / Q000494:pharmacology; D008727:Methotrexate / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors; D013033:Sparsomycin / Q000494:pharmacology*; D014750:Vincristine / Q000494:pharmacology
chemical_list: D000277:Adjuvants, Pharmaceutic; D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D011500:Protein Synthesis Inhibitors; D003561:Cytarabine; D001761:Bleomycin; D014750:Vincristine; D013033:Sparsomycin; D004317:Doxorubicin; D002945:Cisplatin; D008558:Melphalan; D005472:Fluorouracil; D008727:Methotrexate