ENO1 inhibition synergizes with chidamide to induce ferroptosis in PTCL-NOS through metabolic remodeling.

Enolase (ENO1) is a key enzyme involved in glycolysis and plays an important role in various types of cancer. This study explored the role and mechanism of ENO1 and the histone deacetylase inhibitor chidamide in peripheral T cell lymphoma, not otherwise specified (PTCL-NOS). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of ENO1 in human peripheral blood mononuclear cells and PTCL-NOS cell lines (Karpas299, Hut78, and Jurkat). The expression of ENO1 in PTCL-NOS tumor samples was analyzed using a tumor microarray database. Cell proliferation was assessed using Cell Counting Kit-8 (CCK-8) and colony formation assays, and cell migration was examined using Transwell assays. Flow cytometry was used to detect apoptosis, cell cycle progression, and reactive oxygen species, and related proteins were detected by western blotting. Glucose uptake, lactate production, adenosine triphosphate (ATP)/adenosine diphosphate (ADP) ratio, and total iron content were measured using the corresponding assay kits. An in vivo subcutaneous PTCL-NOS tumor model was established in mice to observe their biological behavior. We found that ENO1 was upregulated in PTCL-NOS tissues and cells and its expression was associated with lymph node metastasis. Knockdown of ENO1 activated AMPK, triggered autophagy, and promoted ferroptosis. Chidamide combined with ENO1 knockdown enhanced the effect of the inhibitor on promoting apoptosis and cell cycle arrest in PTCL-NOS tumor cells. Taken together, the findings suggest that knockdown of ENO1 activates autophagy and promotes ferroptosis, thereby inhibiting PTCL-NOS cell proliferation.