增加泛泛素化对于多种类型的癌细胞的生存有益。泛泛素化的抑制有潜力对口腔癌细胞产生抗癌效果，但在口腔癌细胞中的评估较少。本研究旨在调查一种泛泛素化抑制剂MLN4924（pevonedistat）对口腔癌细胞的抗增殖潜力。MLN4924对口腔癌细胞的细胞存活率的抑制效果要高于正常口腔细胞（HGF-1），即口腔癌细胞（CAL 27，OC-2和Ca9-22）的IC50值为1.8，1.4和1.9 μM。MLN4924导致口腔癌细胞的亚G1积累、血管内皮素V的激活、泛caspase和caspases 3/8/9的激活等凋亡性变化的程度远高于正常口腔细胞。MLN4924通过上调活性氧和线粒体超氧化物、降低线粒体膜电位和谷胱甘肽，导致口腔癌细胞比正常细胞产生更大程度的氧化应激。在口腔癌细胞中，也出现了对DNA损伤（γH2AX和8-氧-2'-脱氧鸟苷）的有选择性诱导。因此，本研究表明，MLN4924是一种潜在的抗口腔癌剂，对凋亡的抑制和DNA损伤的促进具有偏爱效果，对正常细胞的细胞毒作用较小。© 2023 Wiley Periodicals LLC.

Increased neddylation benefits the survival of several types of cancer cells. The inhibition of neddylation has the potential to exert anticancer effects but is rarely assessed in oral cancer cells. This study aimed to investigate the antiproliferation potential of a neddylation inhibitor MLN4924 (pevonedistat) for oral cancer cells. MLN4924 inhibited the cell viability of oral cancer cells more than that of normal oral cells (HGF-1) with 100% viability, that is, IC50 values of oral cancer cells (CAL 27, OC-2, and Ca9-22) are 1.8, 1.4, and 1.9 μM. MLN4924 caused apoptotic changes such as the subG1 accumulation, activation of annexin V, pancaspase, and caspases 3/8/9 of oral cancer cells at a greater rate than in normal oral cells. MLN4924 induced greater oxidative stress in oral cancer cells compared to normal cells by upregulating reactive oxygen species and mitochondrial superoxide and depleting the mitochondrial membrane potential and glutathione. In oral cancer cells, preferential inductions also occurred for DNA damage (γH2AX and 8-oxo-2'-deoxyguanosine). Therefore, this investigation demonstrates that MLN4924 is a potential anti-oral-cancer agent showing preferential inhibition of apoptosis and promotion of DNA damage with fewer cytotoxic effects on normal cells.© 2023 Wiley Periodicals LLC.