Fundamental Toxicological Sciences

Paper Details

Fundamental Toxicological Sciences
Vol. 3 No. 3 May 11, 2016 p.115-119
Possible involvement of FosB in (–)-xanthatin-mediated anti-proliferative effects in human cancer MDA-MB-231 cells
  • 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) , Momoko Noguchi 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, FosB, GADD45γ, MDA-MB-231 cells, N-acetyl-L-cysteine, ROS

Cancer cells can develop resistance to anti-cancer agents. Although some mechanisms have been suggested for this resistance to treatments, further detailed research is required. Historically, sesquiterpene lactones (SLs) have been shown to exhibit toxicity in humans and animals due to their chemical nature. Among the SLs identified to date, (–)-xanthatin, which was originally obtained in an extract from Xanthium strumarium, is reportedly less toxic to animals. Furthermore, accumulating evidence suggests that some SLs can kill cancer cells. Therefore, we have focused on (–)-xanthatin and established a method for the chemical synthesis of SLs in order to obtain a pure form. Although we showed that (–)-xanthatin exerts anti-proliferative effects on highly aggressive (poorly differentiated) human MDA-MB-231 breast cancer cells via a mechanism involving the induction of GADD45γ, a tumor suppressor gene, other molecular target(s) of the molecule have not yet been identified. In the present study, we employed chemically synthesized pure (–)-xanthatin to investigate the targets involved in (–)-xanthatin-mediated cell death. The results obtained revealed marked increases in FosB, the expression of which is suggested to be down-regulated in poorly differentiated breast cancers, and the stimulated expression of FosB as well as cell death by (–)-xanthatin was abrogated by N-acetyl-L-cysteine (a ROS-scavenging agent). The possible participation of FosB in (–)-xanthatin-evoked cell death is discussed.