Cell Death Dis: Sidabenamine suppresses cell autophagy through epigenetic modification to fight myeloma activity

The autophagy process of the cell causes abnormal cytoplasm components to produce autophagy small body-dependent lysosome degradation, which involves a series of autophagy-related (ATG) proteins, such as LC3B1-3 as the core of the dynamic remodeling process of the cell membranerecent studies have found that autophagy induction in cells is associated with epigenetic chromatin changes, in particular acetylation (H4K16ac) of histone H4 16th lysine and trimethylation (H3K27me3) of histone H3 27th lysineHistone modifiers (hMOF, SIRT1, and EZH2) have been shown to be key regulators for cellular autophagy reactionsmultiple myeloma (MM) is a plasma cell malignant tumorIn multiple myeloma, the two distinct collaborative protein hydrolysis pathways that inhibit cell autophagy and ubiquitin protease degradation are potentially promising therapeutic strategiesChidamide is a new type of benzoylamide class histone deacetylbase enzyme inhibitor with strong antimyeloma activityin the study, researchers found that sidabenamine has a role in inhibiting cell autophagy in myeloma cellsThe researchers found that the treatment of sidabenamine significantly lowered the expression level of histone deacetylbase SIRT1, while leading to an increase in dose dependence on the expression levels of acetyl transferase hMOF and histone methyl transferase EZH2, which eventually led to an increase in the overall levels of H4K16ac and H3K27me3further experiments found that the levels of H4K16ac and H3K27me3 were raised simultaneously in the promoter region of the autophagy-related gene LC3B, thus enhancing the specific role of these two modifications in the Sidabenamine-mediated LC3B transcription altimepredfinally, the experimental results showed that the combination of the treatment of sidabenamine and protease inhibitor bortezomib showed significant synergetic cytotoxicity for MM cells, which was associated with increased accumulation of uprosin proteins, excessive endogenous mesh stress response, and unfoldd protein reactions of the imbalancethe above results show that sidabenamine can partially inhibit the autophagy degradation of ubiquitin-related cells through epigenetic modification, and in collaboration with boronitomi to enhance antimyeloma activity