Inhibition of TP53 Mutant Oral Cancer by Reactivating p53

Author:

Kang Yei-Jin,Kim Dae-WonORCID,Che Xiangguo,Choi Je-YongORCID,Kim Seong-GonORCID

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.

Funder

Rural Development Administration

Publisher

MDPI AG

Subject

Fluid Flow and Transfer Processes,Computer Science Applications,Process Chemistry and Technology,General Engineering,Instrumentation,General Materials Science

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