Involvement of mitophagy-mediated cell death in colon cancer cells by folate-appended methyl-β-cyclodextrin

  • Khaled M. Elamin
  • Yuki Yamashita
  • Keiichi Motoyama
  • Taishi Higashi
  • Hidetoshi Arima
Original Article


In recent years, colorectal cancer has gained great attention among various types of cancers. We previously synthesized folate-appended methyl-β-cyclodextrin (FA-M-β-CyD) as a novel autophagic antitumor agent. In this study, to further elucidate the impact of FA-M-β-CyD as an antitumor agent, we evaluated cytotoxic activity and the antiproliferative effect in colon cancer cells and colorectal cancer model mice, respectively. As a result, FA-M-β-CyD showed potent cytotoxic activity in HCT116 cells, a human colon cancer cell line, through folate receptor-α (FR-α)-mediated cellular uptake. In addition, FA-M-β-CyD elicited autophagosome formation and induced mitophagy in HCT116 cells. Importantly, FA-M-β-CyD drastically reduced the number of tumor polyps in colorectal cancer model mice induced by azoxymethane/dextran sodium sulfate after intravenous injections once a week for 4 weeks. These results suggest that FA-M-β-CyD has the antiproliferative effect in the colorectal cancer, due to the FR-α-mediated endocytosis and mitophagy induction.


Folate receptor Methyl-β-cyclodextrin Colon cancer Autophagy Targeting 



This work was partially supported by a Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science (16K08198), Center for Clinical and Translational Research of Kyushu University, and a Ministry of Health, Labor, and Welfare Grant-in-Aid for Third Term Comprehensive Control Research for Cancer program (24100701).

Compliance with ethical standards

Conflict of interest

The authors have no conflict of interest directly relevant to the content of this article.


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Copyright information

© Springer Science+Business Media B.V. 2017

Authors and Affiliations

  • Khaled M. Elamin
    • 1
  • Yuki Yamashita
    • 1
    • 2
  • Keiichi Motoyama
    • 1
  • Taishi Higashi
    • 1
  • Hidetoshi Arima
    • 1
    • 2
  1. 1.Department of Physical Pharmaceutics, Graduate School of Pharmaceutical SciencesKumamoto UniversityKumamotoJapan
  2. 2.Program for Leading Graduate Schools “HIGO (Health life science: Interdisciplinary and Glocal Oriented) Program”Kumamoto UniversityKumamotoJapan

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