The neddylation inhibitor MLN4924 inhibits proliferation and triggers apoptosis of oral cancer cells but not for normal cells

Yan Ning Chen, Yu Hsuan Chan, Jun Ping Shiau, Ammad Ahmad Farooqi, Jen Yang Tang, Kuan Liang Chen, Ching Yu Yen, Hsueh Wei Chang

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)299-313
Number of pages15
JournalEnvironmental Toxicology
Volume39
Issue number1
DOIs
Publication statusPublished - Jan 2024

Keywords

  • apoptosis
  • DNA damage
  • neddylation
  • oral cancer cells
  • pevonedistat

ASJC Scopus subject areas

  • Toxicology
  • Management, Monitoring, Policy and Law
  • Health, Toxicology and Mutagenesis

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