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- W4220952021 abstract "ABSTRACT Natural or synthetic naphthoquinones have been identified to interfere with biological systems and, in particular, exhibit anticancer properties. As redox cyclers, they generate reactive oxygen species in cells and, as electrophiles, they react with nucleophiles, mainly thiols, and form covalent adducts. To further decipher the molecular mechanism of action of naphthoquinones in human cells, we analyzed their effects in HeLa cells. First, we demonstrated that the naphthoquinones menadione and plumbagin inhibited the nucleolar NAD+-dependent deacetylase Sirtuin 7 in vitro. As assessed by their inhibition of rDNA transcription, pre-rRNA processing and formation of etoposide-induced 53BP1 foci, menadione and plumbagin also inhibited Sirtuin 7 catalytic activity in vivo. Second, we established that when sulfhydryl arylation by menadione or plumbagin was prevented by the thiol reducing agent N-acetyl-L-cysteine, the inhibition of Sirtuin 7 catalytic activity was also blocked. Finally, we discuss how inhibition of Sirtuin 7 might be crucial in defining menadione or plumbagin as anti-tumor agents that can be used in combination with other anti-tumor strategies." @default.
- W4220952021 created "2022-04-03" @default.
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- W4220952021 date "2022-04-15" @default.
- W4220952021 modified "2023-10-18" @default.
- W4220952021 title "Naphthoquinone-induced arylation inhibits Sirtuin 7 activity" @default.
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- W4220952021 doi "https://doi.org/10.1242/jcs.259207" @default.
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- W4220952021 hasPublicationYear "2022" @default.
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