Journal of Gastroenterology

, Volume 53, Issue 2, pp 197–207 | Cite as

Esophageal cancer stem cells are suppressed by tranilast, a TRPV2 channel inhibitor

  • Atsushi ShiozakiEmail author
  • Michihiro Kudou
  • Daisuke Ichikawa
  • Hitoshi Fujiwara
  • Hiroki Shimizu
  • Takeshi Ishimoto
  • Tomohiro Arita
  • Toshiyuki Kosuga
  • Hirotaka Konishi
  • Shuhei Komatsu
  • Kazuma Okamoto
  • Yoshinori Marunaka
  • Eigo Otsuji
Original Article—Alimentary Tract



Recent evidence suggests that the targeting of membrane proteins specifically activated in cancer stem cells (CSCs) is an important strategy for cancer therapy. The objectives of the present study were to investigate the expression and activity of ion-transport-related molecules in the CSCs of esophageal squamous cell carcinoma.


Cells exhibiting strong aldehyde dehydrogenase 1 family member A1 (ALDH1A1) activity were isolated from TE8 cells by fluorescence-activated cell sorting, and CSCs were then generated with the sphere formation assay. The gene expression profiles of CSCs were examined by microarray analysis.


Among TE8 cells, ALDH1A1 messenger RNA and protein levels were higher in CSCs than in non-CSCs. The CSCs obtained were resistant to cisplatin and had the ability to redifferentiate. The results of the microarray analysis revealed that the expression of 50 genes encoding plasma membrane proteins was altered in CSCs, whereas that of several genes related to ion channels, including transient receptor potential vanilloid 2 (TRPV2), was upregulated. The TRPV2 inhibitor tranilast was more cytotoxic at a lower concentration in CSCs than in non-CSCs, and effectively decreased the number of tumorspheres. Furthermore, tranilast significantly decreased the cell population that strongly expressed ALDH1A1 among TE8 cells.


The results of the present study suggest that TRPV2 is involved in the maintenance of CSCs, and that its specific inhibitor, tranilast, has potential as a targeted therapeutic agent against esophageal squamous cell carcinoma.


Esophageal squamous cell carcinoma Cancer stem cell TRPV2 Tranilast 



This work was supported by a Grant-in-Aid for Scientific Research (C) (26461988) and Grants-in-Aid for Young Scientists (B) (15K19903, 15K19904) from the Japan Society for the Promotion of Science.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

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Copyright information

© Japanese Society of Gastroenterology 2017

Authors and Affiliations

  • Atsushi Shiozaki
    • 1
    Email author
  • Michihiro Kudou
    • 1
  • Daisuke Ichikawa
    • 1
  • Hitoshi Fujiwara
    • 1
  • Hiroki Shimizu
    • 1
  • Takeshi Ishimoto
    • 1
  • Tomohiro Arita
    • 1
  • Toshiyuki Kosuga
    • 1
  • Hirotaka Konishi
    • 1
  • Shuhei Komatsu
    • 1
  • Kazuma Okamoto
    • 1
  • Yoshinori Marunaka
    • 2
    • 3
  • Eigo Otsuji
    • 1
  1. 1.Division of Digestive Surgery, Department of SurgeryKyoto Prefectural University of MedicineKyotoJapan
  2. 2.Department of Molecular Cell Physiology and Bio-Ionomics, Graduate School of Medical ScienceKyoto Prefectural University of MedicineKyotoJapan
  3. 3.Japan Institute for Food Education and HealthSt. Agnes’ UniversityKyotoJapan

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