Glycolysis inhibition sensitizes tumor cells to death receptors-induced apoptosis by AMP kinase activation leading to Mcl-1 block in translation.

摘要: Most cancer cells exhibit increased glycolysis for generation of their energy supply. This specificity could be used to preferentially kill these cells. In this study, we identified the signaling pathway initiated by inhibition that results in sensitization death receptor (DR)-induced apoptosis. We showed, several human cell lines (such as Jurkat, HeLa, U937), glucose removal or use nonmetabolizable form (2-deoxyglucose) dramatically enhances apoptosis induced Fas tumor necrosis factor-related apoptosis-inducing ligand. is controlled through adenosine monophosphate (AMP)-activated protein kinase (AMPK), which central energy-sensing system cell. established fact AMPK activated upon block resulting mammalian target rapamycin (mTOR) leading Mcl-1 decrease, but no other Bcl-2 anti-apoptotic members. Interestingly, determined that, inhibition, AMPK-mTOR levels neither transcriptional nor posttranslational mechanism rather controlling its translation. Therefore, our show a novel DR-induced linking metabolism downexpression. addition, study provides rationale combined DR ligands with activators mTOR inhibitors treatment cancers.