Increased Activity and Sensitivity of Mitochondrial Respiratory Enzymes to Tumor Necrosis Factor a-Mediated Inhibition Is Associated With Increased Cytotoxicity in Drug-Resistant Leukemic Cell Lines
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چکیده
The drug-resistant leukemic cell lines, CEM/VLBlm and K/ DAU-, are more sensitive to tumor necrosis factor a (TNFa)-mediated cytotoxicity compared with their parental cell lines, CCRF-CEM and K562 c1.6. Drugresistant leukemic cell lines have more active mitochondrial function, which is associated with a greater susceptibility to TNFa-induced respiratory inhibition. TNFa blocked electron transfer at three sites, NADH dehydrogenase (complex I), succinate dehydrogenase (complex 11). and cytochrome c oxidase (complex IV). Respiratory rate and electron transport chain enzyme activities were significantly inhibited in the drugresistant, TNF-sensitive cell lines. Respiratory inhibition preceded cell death by at least 5 to 8 hours. The respiratory failure was not compensated for by appropriate up-regula-
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