Fructose sensitizes Jurkat cells oxidative stress-induced apoptosis via caspase-dependent and caspase-independent mechanisms

摘要: Whether fructose (FRU), as the sole energy source, confers a metabolic advantage on cancer cells against noxious stimuli is unknown. The aim of this study was to evaluate effects low (11 mM), moderate (25 mM), and high (55 mM) FRU concentrations alone or in combination with rotenone (ROT) doxorubicin (DOX) Jurkat cells, an acute lymphoblastic leukemia cell model. Glucose (GLU) used control. Using different analysis techniques, we demonstrated that predominantly metabolized via oxidative phosphorylation (∼95%) (i.e., lactate production reduced >120-fold), resulting endogenous stress-induced conditions. were characterized by generation O2•− (43%)/ H2O2 (40%) activation NF-κB (∼95-fold increase, fi), c-Jun-N terminal kinase (JNK), p53 (40-fi), c-Jun (9-fi). In addition, observed loss ΔΨm (10%), caspase-3 (50-fi) apoptosis-inducing factor (AIF, 2-fi), condensation fragmentation nuclei [20% acridine orange/ethidium bromide/Hoechst (AO/EB/H) staining, 15% flow cytometry] compared those GLU 11 at 24 h. Although DOX killed independent sugar content culture medium, leukemic low, but not high, extremely sensitive ROT. Taken together, our findings suggest are more susceptible death if forced shift from metabolism aerobic glycolysis) phosphorylation) after treatment mitochondria-targeting molecules. These observations may help elucidate mechanism cultured FRU.