Fundamental Toxicological Sciences

Paper Details

Fundamental Toxicological Sciences
Vol. 2 No. 6 December 12, 2015 p.233-238
(–)-Xanthatin-mediated marked up-regulation of RhoB, a sensor for damaged DNA
  • Hironori Aramaki (Department of Molecular Biology, Daiichi University of Pharmacy / Drug Innovation Research Center, Daiichi University of Pharmacy /
Shuso Takeda 1) 2) , Shunsuke Okajima 1) , Hiroko Miyoshi 1) , Kuniyoshi Koyachi 3) , Kenji Matsumoto 4) , Mitsuru Shindo 4) , Hironori Aramaki 1) 5)
1) Department of Molecular Biology, Daiichi University of Pharmacy , 2) Laboratory of Xenobiotic Metabolism and Environmental Toxicology, Faculty of Pharmaceutical Sciences, Hiroshima International University (HIU) , 3) Interdisciplinary Graduate School of Engineering Sciences, Kyushu University , 4) Institute for Materials Chemistry and Engineering, Kyushu University , 5) Drug Innovation Research Center, Daiichi University of Pharmacy
Keywords: (–)-Xanthatin, RhoB, GADD45γ, MDA-MB-231 cells, Topoisomerase IIα, ROS

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.