Transglutaminase 2 inhibitor abrogates renal cell carcinoma in xenograft models

  • Bo Mi Ku
  • Se-Jin Kim
  • Nayeon Kim
  • Dongwan Hong
  • Yong-Bock Choi
  • Seon-Hyeong Lee
  • Young-Dae GongEmail author
  • Soo-Youl KimEmail author
Original Article - Cancer Research



To test whether transglutaminase 2 (TGase 2) inhibitor GK921 alone reverses renal cell carcinoma (RCC) tumor growth. RCC is resistant to both radiation and chemotherapy, and the prognosis remains poor. Despite the recent therapeutic success of vascular endothelial growth factor inhibition in RCC, approximately one-third of RCC patients develop metastatic disease. The expression of TGase 2 is markedly increased in most RCC cell lines, as well as in clinical samples.


Previously, we introduced the quinoxaline derivative GK13 as a lead compound for TGase 2 inhibitor. The inhibitory effect of GK13 on TGase 2 was improved in GK921 (3-(phenylethynyl)-2-(2-(pyridin-2-yl)ethoxy)pyrido[3,2-b]pyrazine). GK921 efficacy was tested using sulforhodamine in vitro as well as a xenograft tumor models using ACHN and CAKI-1 RCC cells.


GK921 showed cytotoxicity to RCC (average GI50 in eight RCC cell lines: 0.905 μM). A single treatment with GK921 almost completely reduced tumor growth by stabilizing p53 in the ACHN and CAKI-1 preclinical xenograft tumor models.


TGase 2 inhibitor GK921 abrogates RCC growth in xenograft tumor models, suggesting the possibility of a new therapeutic approach to RCC.


Transglutaminase 2 Renal cell carcinoma TGase 2 inhibitor p53 



Transglutaminase 2


Renal cell carcinoma


Sulforhodamine B


NF-κ-B inhibitor α



The study was supported by a research grant (NCC1410280-1) from the National Cancer Center of Korea to S. Y. K. The study was supported by the National R&D Program for Cancer Control (No. 1020050) of Korea to Y. D. G.

Conflict of interest

The authors declare no conflict of interest.

Ethical standards

The experiments comply with the current laws of Korea.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Bo Mi Ku
    • 1
  • Se-Jin Kim
    • 1
  • Nayeon Kim
    • 3
  • Dongwan Hong
    • 2
  • Yong-Bock Choi
    • 1
  • Seon-Hyeong Lee
    • 1
  • Young-Dae Gong
    • 3
    Email author
  • Soo-Youl Kim
    • 1
    Email author
  1. 1.Cancer Cell and Molecular Biology Branch, Division of Cancer Biology, Research InstituteNational Cancer CenterGoyangRepublic of Korea
  2. 2.Cancer Genomics Branch, Division of Convergence Technology, Research InstituteNational Cancer CenterGoyangRepublic of Korea
  3. 3.Center for Innovative Drug Library ResearchDongguk UniversitySeoulRepublic of Korea

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