Archives of Pharmacal Research

, Volume 39, Issue 6, pp 825–832 | Cite as

Characterization of the cytotoxic activity of [2]rotaxane (TRO-A0001), a novel supramolecular compound, in cancer cells

  • Yoshihiko Fujita
  • Masahiko Kimura
  • Hiroki Sato
  • Toshikazu Takata
  • Nobufumi Ono
  • Kazuto NishioEmail author
Research Article


Rotaxanes comprise a class of interlocked molecules containing a wheel threaded onto an axle with blocking groups on the ends to keep the wheel from sliding off. Here, we show that [2][bis(2-(3,5-dimethylphenylcarbonyloxy)ethyl) ammoniumtrifluoromethanesulfonate]-[dibenzo-24-crown-8] rotaxane (TRO-A0001), a rotaxane compound, exerted a growth inhibitory effect on several human cancer cell lines. An MTT assay revealed an IC50 of 14-830 nM for TRO-A0001 in these cells. Neither the wheel nor the axle part alone inhibited tumor cell growth, suggesting that the complete rotaxane molecule with its unique “intramolecular mobility” is required to inhibit cell growth. Annexin-V/PI staining provided evidence of the induction of apoptosis, which was further confirmed by the observation of poly (ADP-ribose) polymerase cleavage. Furthermore, a cell cycle analysis using flow cytometry showed that TRO-A0001 treatment resulted in G1 arrest in glioblastoma T98G and melanoma G361 cells. An immunoblot analysis revealed that in both cell lines, TRO-A0001 treatment caused the induction of p21/Cip1, thereby down-regulating Cdks 2, 4 and 6 and reducing Cyclins D1 and E. The results presented in this study demonstrate cytotoxicity of the rotaxane compound and its potential as a lead compound for the development of a chemotherapeutic agent against cancer.


Rotaxane Supramolecular compound Cancer G1 cell-cycle arrest p21/Cip1 Apoptosis 



This work was supported by the Grant-in-Aid for Scientific Research (C) (Grant No. 25350979) of Ministry of Education, Culture, Sports, Science and Technology of Japan. We thank Kurashimo S. and Kitayama T. for technical support and Marco A. De Velasco for critically reading the manuscript.

Compliance with ethical standards

Conflict of interest

All authors have no conflicts of interest to disclose.


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Copyright information

© The Pharmaceutical Society of Korea 2016

Authors and Affiliations

  • Yoshihiko Fujita
    • 1
  • Masahiko Kimura
    • 2
  • Hiroki Sato
    • 3
  • Toshikazu Takata
    • 3
  • Nobufumi Ono
    • 4
  • Kazuto Nishio
    • 1
    Email author
  1. 1.Department of Genome BiologyKinki University Faculty of MedicineOsakaJapan
  2. 2.Medicinal-Informatics and Research Unit, Faculty of Pharmaceutical SciencesFukuoka UniversityFukuokaJapan
  3. 3.Department of Organic and Polymeric MaterialsTokyo Institute of TechnologyTokyoJapan
  4. 4.Miki Health Science Research InstituteFukuokaJapan

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