TY - JOUR
T1 - Resveratrol and its Related Polyphenols Contribute to the Maintenance of Genome Stability
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
PY - 2020/12/1
Y1 - 2020/12/1
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.
AB - 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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U2 - 10.1038/s41598-020-62292-5
DO - 10.1038/s41598-020-62292-5
M3 - Article
C2 - 32214146
AN - SCOPUS:85082418161
VL - 10
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 5388
ER -