FOXO signaling pathway participates in oxidative stress-induced histone deacetylation

Abstract

High concentrations of antioxidants can exert pro-oxidative effects, elevate the level of intracellular reactive oxygen species (ROS), and cause oxidative stress in cells. We previously found that high concentrations of curcumin, a natural polyphenol antioxidant, elevated ROS levels and upregulated the expression of histone deacetylase 1 (HDAC1) in human gastric cancer cells (hGCCs); however, its potential mechanisms and subsequent functions have not been elucidated. In the present study, we treated hGCCs with high concentrations of curcumin, detected several indicators of oxidative stress, and investigated the mechanism of curcumin-treatment-mediated HDAC1 upregulation and its effect on histone acetylation. The results showed that curcumin treatment caused oxidative stress in hGCCs and upregulated HDAC1/2 expression via the forkhead box O (FOXO) signaling pathway, ultimately leading to the deacetylation of histones in hGCCs. Moreover, HDAC1/2 mediates the deacetylation of FOXOs and promotes their transcription activities, implying a positive feedback loop between FOXOs and HDAC1/2. These findings present a mechanism by which oxidative stress induces histone deacetylation in hGCCs.

Keywords:

• Oxidative stress
• histone acetylation
• FOXO signaling pathway
• curcumin
• human gastric cancer cells

Acknowledgements

The authors thank Dr. Chuncheng Liu for technical assistance.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The raw data used to support the findings of this study are deposited into figshare database, DOI: 10.6084/m9.figshare. 21835677.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China under Grant [number: 31660340, 31560331]; Natural Science Foundation of Inner Mongolia Autonomous Region of China under Grant [number: 2022MS03017, 2020BS03004, 2021BS03014, 2021LHBS03002]; and Research Program of Science and Technology at Universities of Inner Mongolia Autonomous Region of China under Grant [number: NJZZ20087, NJZY21386].