Increased sensitivity of an adriamycin-resistant human small cell lung carcinoma cell line to mitochondrial inhibitors.
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.
de Jong
S
S
Department of Internal Medicine, University of Groningen, The Netherlands.
Holtrop
M
M
de Vries
H
H
de Vries
E G
EG
Mulder
N H
NH
D000255:Adenosine Triphosphate / Q000378:metabolism; D015152:Blotting, Northern; D018288:Carcinoma, Small Cell; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003847:Deoxyglucose / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology*; D004318:Doxycycline / Q000494:pharmacology*; D004351:Drug Resistance; D003576:Electron Transport Complex IV / Q000235:genetics; D004734:Energy Metabolism / Q000187:drug effects*; D005456:Fluorescent Dyes; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D007773:Lactates / Q000378:metabolism; D008175:Lung Neoplasms; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D009840:Oligomycins / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D020112:Rhodamine 123; D012235:Rhodamines / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects
D005456:Fluorescent Dyes; D007773:Lactates; D009840:Oligomycins; D012334:RNA, Neoplasm; D012235:Rhodamines; D020112:Rhodamine 123; D009249:NADP; D004317:Doxorubicin; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D005954:Glucosephosphate Dehydrogenase; D003576:Electron Transport Complex IV; D004318:Doxycycline