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Transglutaminase 2 inhibitor abrogates renal cell carcinoma in xenograft models

  • Original Article - Cancer Research
  • Published:
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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusion

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

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Abbreviations

TGase2:

Transglutaminase 2

RCC:

Renal cell carcinoma

SRB:

Sulforhodamine B

I-κBα:

NF-κ-B inhibitor α

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Acknowledgments

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.

Author information

Authors and Affiliations

  1. Cancer Cell and Molecular Biology Branch, Division of Cancer Biology, Research Institute, National Cancer Center, Goyang, Republic of Korea

    Bo Mi Ku, Se-** Kim, Yong-Bock Choi, Seon-Hyeong Lee & Soo-Youl Kim

  2. Cancer Genomics Branch, Division of Convergence Technology, Research Institute, National Cancer Center, Goyang, Republic of Korea

    Dongwan Hong

  3. Center for Innovative Drug Library Research, Dongguk University, Seoul, Republic of Korea

    Nayeon Kim & Young-Dae Gong

Authors
  1. Bo Mi Ku
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  2. Se-** Kim
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  3. Nayeon Kim
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  6. Seon-Hyeong Lee
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  7. Young-Dae Gong
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Corresponding authors

Correspondence to Young-Dae Gong or Soo-Youl Kim.

Additional information

Bo Mi Ku and Se-** Kim have contributed equally to this work.

This article published in the Journal of Cancer Research and Clinical Oncology, Volume 140, Issue 5, pages 757-767, 10.1007/s00432-014-1623-5, has been retracted at the request of the Editor-in-Chief as it is a duplicate of a paper that has already been published in: Cancer Science & Therapy Volume 5, Issue 10, pages 368-376 10.4172/1948-5956.1000228.

At the time the decision for retraction was made this article appeared to be a duplicate publication. When the authors were informed their withdrawal from a previous publication had not been completed, the duplicate article was immediately removed. Retraction of this article has been rescinded as it is the original version.

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Ku, B.M., Kim, SJ., Kim, N. et al. Transglutaminase 2 inhibitor abrogates renal cell carcinoma in xenograft models. J Cancer Res Clin Oncol 140, 757–767 (2014). https://doi.org/10.1007/s00432-014-1623-5

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