Fundamental Toxicological Sciences
Online ISSN : 2189-115X
ISSN-L : 2189-115X
Letter
(–)-Xanthatin-mediated marked up-regulation of RhoB, a sensor for damaged DNA
Shuso TakedaShunsuke OkajimaHiroko MiyoshiKuniyoshi KoyachiKenji MatsumotoMitsuru ShindoHironori Aramaki
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2015 年 2 巻 6 号 p. 233-238

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抄録
Sesquiterpene lactones exhibit toxicity in humans and animals by non-selectively interacting with cellular macromolecules. Among the sesquiterpene lactones identified to date, (–)-xanthatin, which was obtained in an extract from Xanthium strumarium (the Cocklebur plant), is reportedly less toxic to animals. Although we have shown that (–)-xanthatin has anti-proliferative effects, coupled with the induction of DNA damage-inducible GADD45γ, on highly aggressive human MDA-MB-231 breast cancer cells, the molecular mechanisms of anti-proliferative activity have not yet been elucidated in detail. Furthermore, evidence for the involvement of DNA damage is currently not sufficient. In the present study, we chemically synthesized pure (–)-xanthatin, and attempted to obtain more concrete evidence for DNA damage caused by (–)-xanthatin, which leads to cell death. The results obtained revealed the marked up-regulation of RhoB, which is up-regulated by DNA damage. We summarized the anti-proliferative effects of (–)-xanthatin in combination with our previous findings.
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© 2015 The Japanese Society of Toxicology
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