Histone deacetylases (HDACs) inhibit the acetylation of crucial autophagy genes, thereby deregulating autophagy and autophagic cell death (ACD) and facilitating cancer cell survival. Vorinostat, a broad-spectrum pan-HDAC inhibitor, inhibits the deacetylation of key autophagic markers and thus interferes with ACD. Vorinostat-regulated ACD can have an autophagy-mediated, -associated or -dependent mechanism depending on the involvement of apoptosis. Molecular insights revealed that hyperactivation of the PIK3C3/VPS34–BECN1 complex increases lysosomal disparity and enhances mitophagy. These changes are followed by reduced mitochondrial biogenesis and by secondary signals that enable superactivated, nonselective or bulk autophagy, leading to ACD. Although the evidence is limited, this review focuses on molecular insights into vorinostat-regulated ACD and describes critical concepts for clinical translation.

组蛋白脱乙酰酶 (HDAC) 抑制关键自噬基因的乙酰化，从而解除对自噬和自噬细胞死亡 (ACD) 的调节，并促进癌细胞存活。Vorinostat 是一种广谱泛 HDAC 抑制剂，可抑制关键自噬标记物的去乙酰化，从而干扰 ACD。取决于细胞凋亡的参与，伏立诺他调节的 ACD 可以具有自噬介导的、相关的或依赖的机制。分子洞察显示 PIK3C3/VPS34–BECN1 复合物的过度活化增加了溶酶体差异并增强了线粒体自噬。这些变化之后是线粒体生物发生减少和次级信号，这些次级信号使超活化、非选择性或大量自噬成为可能，从而导致 ACD。虽然证据有限，