Resveratrol and its Related Polyphenols Contribute to the Maintenance of Genome Stability

Yusuke Matsuno; Yuko Atsumi; Md Alauddin; Md Masud Rana; Haruka Fujimori; Mai Hyodo; Atsuhiro Shimizu; Tomoki Ikuta; Hiroko Tani; Hidetaka Torigoe; Yoshimichi Nakatsu; Teruhisa Tsuzuki; Michio Komai; Hitoshi Shirakawa; Ken ichi Yoshioka

doi:10.1038/s41598-020-62292-5

Resveratrol and its Related Polyphenols Contribute to the Maintenance of Genome Stability

Yusuke Matsuno, Yuko Atsumi, Md Alauddin, Md Masud Rana, Haruka Fujimori, Mai Hyodo, Atsuhiro Shimizu, Tomoki Ikuta, Hiroko Tani, Hidetaka Torigoe, Yoshimichi Nakatsu, Teruhisa Tsuzuki, Michio Komai, Hitoshi Shirakawa, Ken ichi Yoshioka

Bioregulation

Research output: Contribution to journal › Article › peer-review

14 Citations (Scopus)

Abstract

Genomic destabilisation is associated with the induction of mutations, including those in cancer-driver genes, and subsequent clonal evolution of cells with abrogated defence systems. Such mutations are not induced when genome stability is maintained; however, the mechanisms involved in genome stability maintenance remain elusive. Here, resveratrol (and related polyphenols) is shown to enhance genome stability in mouse embryonic fibroblasts, ultimately protecting the cells against the induction of mutations in the ARF/p53 pathway. Replication stress-associated DNA double-strand breaks (DSBs) that accumulated with genomic destabilisation were effectively reduced by resveratrol treatment. In addition, resveratrol transiently stabilised the expression of histone H2AX, which is involved in DSB repair. Similar effects on the maintenance of genome stability were observed for related polyphenols. Accordingly, we propose that polyphenol consumption can contribute to the suppression of cancers that develop with genomic instability, as well as lifespan extension.

Original language	English
Article number	5388
Journal	Scientific reports
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41598-020-62292-5
Publication status	Published - Dec 1 2020

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Matsuno, Y., Atsumi, Y., Alauddin, M., Rana, M. M., Fujimori, H., Hyodo, M., Shimizu, A., Ikuta, T., Tani, H., Torigoe, H., Nakatsu, Y., Tsuzuki, T., Komai, M., Shirakawa, H., & Yoshioka, K. I. (2020). Resveratrol and its Related Polyphenols Contribute to the Maintenance of Genome Stability. Scientific reports, 10(1), [5388]. https://doi.org/10.1038/s41598-020-62292-5

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abstract = "Genomic destabilisation is associated with the induction of mutations, including those in cancer-driver genes, and subsequent clonal evolution of cells with abrogated defence systems. Such mutations are not induced when genome stability is maintained; however, the mechanisms involved in genome stability maintenance remain elusive. Here, resveratrol (and related polyphenols) is shown to enhance genome stability in mouse embryonic fibroblasts, ultimately protecting the cells against the induction of mutations in the ARF/p53 pathway. Replication stress-associated DNA double-strand breaks (DSBs) that accumulated with genomic destabilisation were effectively reduced by resveratrol treatment. In addition, resveratrol transiently stabilised the expression of histone H2AX, which is involved in DSB repair. Similar effects on the maintenance of genome stability were observed for related polyphenols. Accordingly, we propose that polyphenol consumption can contribute to the suppression of cancers that develop with genomic instability, as well as lifespan extension.",

author = "Yusuke Matsuno and Yuko Atsumi and Md Alauddin and Rana, {Md Masud} and Haruka Fujimori and Mai Hyodo and Atsuhiro Shimizu and Tomoki Ikuta and Hiroko Tani and Hidetaka Torigoe and Yoshimichi Nakatsu and Teruhisa Tsuzuki and Michio Komai and Hitoshi Shirakawa and Yoshioka, {Ken ichi}",

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doi = "10.1038/s41598-020-62292-5",

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AU - Matsuno, Yusuke

AU - Atsumi, Yuko

AU - Alauddin, Md

AU - Rana, Md Masud

AU - Fujimori, Haruka

AU - Hyodo, Mai

AU - Shimizu, Atsuhiro

AU - Ikuta, Tomoki

AU - Tani, Hiroko

AU - Torigoe, Hidetaka

AU - Nakatsu, Yoshimichi

AU - Tsuzuki, Teruhisa

AU - Komai, Michio

AU - Shirakawa, Hitoshi

AU - Yoshioka, Ken ichi

N1 - Funding Information: This study is supported by Yamada Research Grant, Japan Coffee Association, The Tojuro Iijima Foundation for Food Science and Technology, Mishima Kaiun Memorial Foundation, and the JSPS Core-to-Core Program A (Advanced Research Networks) entitled: “Establishment of international agricultural immunology research-core for a quantum improvement in food safety”. This work is also supported by Yamada Bee Company Inc. Publisher Copyright: © 2020, The Author(s).

PY - 2020/12/1

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N2 - Genomic destabilisation is associated with the induction of mutations, including those in cancer-driver genes, and subsequent clonal evolution of cells with abrogated defence systems. Such mutations are not induced when genome stability is maintained; however, the mechanisms involved in genome stability maintenance remain elusive. Here, resveratrol (and related polyphenols) is shown to enhance genome stability in mouse embryonic fibroblasts, ultimately protecting the cells against the induction of mutations in the ARF/p53 pathway. Replication stress-associated DNA double-strand breaks (DSBs) that accumulated with genomic destabilisation were effectively reduced by resveratrol treatment. In addition, resveratrol transiently stabilised the expression of histone H2AX, which is involved in DSB repair. Similar effects on the maintenance of genome stability were observed for related polyphenols. Accordingly, we propose that polyphenol consumption can contribute to the suppression of cancers that develop with genomic instability, as well as lifespan extension.

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Resveratrol and its Related Polyphenols Contribute to the Maintenance of Genome Stability

Abstract

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