1. Inhibition of TP53 Mutant Oral Cancer by Reactivating p53
- Author
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Yei-Jin Kang, Dae-Won Kim, Xiangguo Che, Je-Yong Choi, and Seong-Gon Kim
- Subjects
4-hexylresorcinol ,p53 ,phosphorylation ,acetylation ,Technology ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Biology (General) ,QH301-705.5 ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
Background: Mutation of p53 is a frequent event, and mutant p53 exhibits low levels of acetylation and phosphorylation. This study aimed to investigate the effect of the histone deacetylase (HDAC) inhibitor, 4-hexylresorcinol (4HR), on the acetylation and phosphorylation of mutant p53 carcinoma cells and its therapeutic effects in a xenograft model. Methods: To determine the effect of 4HR on the acetylation and phosphorylation of p53, western blot analysis was performed using YD-9 and YD-15 cells. p53 siRNA was used to examine whether 4HR acts in a p53-dependent or independent manner. This was evaluated using a xenograft model. Results: In in vitro experiments when the concentration of 4HR was increased, the expression levels of HDAC4, acetylated p53 (Ac-p53), and phosphorylated p53 (p-p53) increased. Transfection with TP53 siRNA successfully suppressed p53 protein and TP53 mRNA expression. When 4HR was administered to a xenograft model, the tumour expansion rate was suppressed compared with the control, and the mice exhibited a higher survival rate. Conclusions: Our findings reveal that 4HR is a potential agent that restores loss of function in mutant p53 cancer cells via acetylation and phosphorylation of p53 as well as inhibition of HDAC4. more...
- Published
- 2022
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