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Sirtuin1 (SIRT1) is involved in the anticancer effect of black raspberry anthocyanins in colorectal cancer

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Abstract

Purpose

Abnormal acetylation modification is a common epigenetic change in tumorigenesis and is closely related to the progression of colorectal cancer (CRC). Our previous studies have suggested that black raspberry (BRB) anthocyanins have a significant chemopreventive effect against CRC. This study investigated whether protein acetylation plays an important role in BRB anthocyanins-mediated regulation of CRC progression.

Methods

We used the AOM-induced CRC mouse model and the CRC cell lines SW480 and Caco-2 to explore the potential role of acetylation of histone H4 and NF-κB signaling pathway-related proteins (non-histone proteins) in the antitumor process mediated by BRB anthocyanins. The expression of related proteins was detected by western blot. ROS level was detected by immunofluorescence.

Results

BRB anthocyanins affected the acetylation level by down-regulating the expression of Sirtuin1 (SIRT1) and up-regulating the expression of MOF and EP300. The acetylation level of lysine sites on histone H4 (H4K5, H4K12 and H4K16) was increased. Furthermore, following BRB anthocyanins treatment, the expression of ac-p65 was significantly up-regulated and the NF-κB signal pathway was activated, which in turn up-regulated Bax expression and inhibited Bcl-2, cyclin-D1, c-myc and NLRP3 expression to promote CRC cell cycle arrest, apoptosis and relieve inflammation.

Conclusion

The findings suggested that protein acetylation could play a critical role in BRB anthocyanins-regulated CRC development.

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Acknowledgements

This work was mainly supported by the Grants from National Natural Science Foundation of China (Grants#81272333; #81472821), Liaoning Revitalization Talents Program (#XLYC1807058), Key Grant of Basic Research Liaoning Education Department (LETU#LZD201904) to Bi, X, Disciplinary Construction Project of the College of Mathematics and Statistics, Liaoning University (MSKY202210) to Chen, L. We thank Dr. Alan K. Chang for revising the language of the manuscript.

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Author notes

  1. Lili Chen, Mei Li, and Hongrui Zhou contributed equally to this work.

Authors and Affiliations

  1. College of Life Science, Liaoning University, 66 Chongshan Road, Shenyang, 110036, China

    Lili Chen, Mei Li, Hongrui Zhou, Yue Liu, Wenqian Pang, Teng Ma, Chang Niu, Zhe Yang & Xiuli Bi

  2. College of Mathematics and Statistics, Liaoning University, Shenyang, 110036, China

    Lili Chen

  3. College of Life and Environmental Sciences, Wenzhou University, Wenzhou, 325035, China

    Alan K. Chang

  4. Shenzhen Fushan Biological Technology Co., Ltd, Kexing Science Park A1 1005, Nanshan Zone, Shenzhen, 518057, China

    Xiaolong Li

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  1. Lili Chen
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Contributions

XB and LC designed the research. ML and HZ wrote the original manuscript, XB, LC and AC reviewed and edited the manuscript. LC, YL, WP, TM and CN performed the experiments. LC, ZY and XL analyzed the data. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Xiuli Bi.

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Conflict of interest

The authors declare no conflict of interest.

Ethics approval

All animal procedures performed were approved by the Animal Care Committee of the Traditional Chinese Medicine of Liaoning University (No. 21000092017048).

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Chen, L., Li, M., Zhou, H. et al. Sirtuin1 (SIRT1) is involved in the anticancer effect of black raspberry anthocyanins in colorectal cancer. Eur J Nutr 62, 395–406 (2023). https://doi.org/10.1007/s00394-022-02989-7

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  • DOI: https://doi.org/10.1007/s00394-022-02989-7

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