oligomycins and Carcinoma--Small-Cell

The energy metabolism of an atypical multidrug resistant human small cell lung carcinoma cell line (GLC4/ADR) was studied. The glycolytic rate was 30% reduced and the glucose-6-phosphate dehydrogenase activity 2-fold increased in GLC4/ADR compared to the parental sensitive line (GLC4). Although mitochondrial respiration activities were similar in both cell lines, GLC4/ADR was more sensitive to the antimitochondrial drugs doxycycline and oligomycin, while cross-resistance was observed for the glycolytic inhibitor 2-deoxyglucose and for the antimitochondrial drug rhodamine-123. Continuous incubation with doxycycline induced a dramatic reduction of mitochondrial mRNAs in both cell lines, whereas a strong reduction of the nuclear-coded mRNA for subunit IV of cytochrome c oxidase was induced in GLC4/ADR only. Incubation with doxycycline had an additive effect on the cytotoxicity of adriamycin in both cell lines. Thus, a form of collateral sensitivity to antimitochondrial drugs may exist in atypical multidrug resistant cell lines.

Topics: Adenosine Triphosphate; Blotting, Northern; Carcinoma, Small Cell; Cell Line; Cell Survival; Deoxyglucose; Doxorubicin; Doxycycline; Drug Resistance; Electron Transport Complex IV; Energy Metabolism; Fluorescent Dyes; Glucosephosphate Dehydrogenase; Glycolysis; Humans; Kinetics; Lactates; Lung Neoplasms; Mitochondria; NADP; Oligomycins; Oxygen Consumption; Rhodamine 123; Rhodamines; RNA, Neoplasm; Transcription, Genetic