Reversal of TNF-α resistance by hyperthermia: Role of mitochondria

The aim of this study is to examine the effect of hyperthermia on tumour necrosis factor-α (TNF-α) resistance in L929-11E cells. L929-11E is a TNF-α resistant variant derived from L929 cells, a commonly used model for TNF-α study. Based on the results from flow cytometry and Western blotting, hyperthermia (43°C, 3h) was found to induce apoptosis, mitochondrial potential (ΔΨm) depolarization and release of cytochrome c in L929-11E cells. Similar responses were found in L929 cells when treated with TNF-α. Heating at 43°C for 1h did not significantly damage the mitochondria of L929-11E cells but partially reversed their resistance to TNF-α. When L929-11E cells were sequentially treated with heating (43°C, 1h) and TNF-α, a more severe damage in mitochondria was observed. Taken together, our results indicate (1) hyperthermia induced apoptosis in L929-11E cells via mitochondrial damages in a way very similar to the action of TNF-α in L929 cells, (2) hyperthermia could be used to overcome TNF-α resistance by altering mitochondrial activities and (3) L929-11E and its parental cells provide a useful model in elucidating the signalling linkage between TNF-α receptor and mitochondria.