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Article Open Access

Clinically relevant GSK‑3β inhibitor 9‑ING‑41 is active as a single agent and in combination with other antitumor therapies in human renal cancer

  • Authors:
    • Tsutomu Anraku
    • Hiroo Kuroki
    • Akira Kazama
    • Vladimir Bilim
    • Masaaki Tasaki
    • Daniel Schmitt
    • Andrew Mazar
    • Francis J. Giles
    • Andrey Ugolkov
    • Yoshihiko Tomita
  • View Affiliations / Copyright

    Affiliations: Department of Urology, Division of Molecular Oncology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951‑8510, Japan, Actuate Therapeutics, Fort Worth, TX 76107, USA, Monopar Therapeutics, Wilmette, IL 60091, USA
    Copyright: © Anraku et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 315-323
    |
    Published online on: December 12, 2019
       https://doi.org/10.3892/ijmm.2019.4427
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Abstract

Glycogen synthase kinase‑3 (GSK‑3), a serine/threonine kinase, is involved in a broad range of pathological processes including cancer. GSK‑3 has two isoforms, GSK‑3α and GSK‑3β, and GSK‑3β has been recognized as a therapeutic target for the development of new anticancer drugs. The present study aimed to investigate the antitumor effects of 9‑ING‑41, which is a maleimide‑based ATP‑competitive small molecule GSK‑3β inhibitor active in patients with advanced cancer. In renal cancer cell lines, treatment with 9‑ING‑41 alone induced cell cycle arrest and apoptosis, and autophagy inhibitors increased the antitumor effects of 9‑ING‑41 when used in combination. Treatment with 9‑ING‑41 potentiated the antitumor effects of targeted therapeutics and increased the cytotoxic effects of cytokine‑activated immune cells on renal cancer cell lines. These results provided a compelling rationale for the inclusion of patients with renal cancer in studies of 9‑ING‑41, both as a single agent and in combination with current standard therapies.
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Copy and paste a formatted citation
Spandidos Publications style
Anraku T, Kuroki H, Kazama A, Bilim V, Tasaki M, Schmitt D, Mazar A, Giles FJ, Ugolkov A, Tomita Y, Tomita Y, et al: Clinically relevant GSK‑3β inhibitor 9‑ING‑41 is active as a single agent and in combination with other antitumor therapies in human renal cancer. Int J Mol Med 45: 315-323, 2020.
APA
Anraku, T., Kuroki, H., Kazama, A., Bilim, V., Tasaki, M., Schmitt, D. ... Tomita, Y. (2020). Clinically relevant GSK‑3β inhibitor 9‑ING‑41 is active as a single agent and in combination with other antitumor therapies in human renal cancer. International Journal of Molecular Medicine, 45, 315-323. https://doi.org/10.3892/ijmm.2019.4427
MLA
Anraku, T., Kuroki, H., Kazama, A., Bilim, V., Tasaki, M., Schmitt, D., Mazar, A., Giles, F. J., Ugolkov, A., Tomita, Y."Clinically relevant GSK‑3β inhibitor 9‑ING‑41 is active as a single agent and in combination with other antitumor therapies in human renal cancer". International Journal of Molecular Medicine 45.2 (2020): 315-323.
Chicago
Anraku, T., Kuroki, H., Kazama, A., Bilim, V., Tasaki, M., Schmitt, D., Mazar, A., Giles, F. J., Ugolkov, A., Tomita, Y."Clinically relevant GSK‑3β inhibitor 9‑ING‑41 is active as a single agent and in combination with other antitumor therapies in human renal cancer". International Journal of Molecular Medicine 45, no. 2 (2020): 315-323. https://doi.org/10.3892/ijmm.2019.4427
Copy and paste a formatted citation
x
Spandidos Publications style
Anraku T, Kuroki H, Kazama A, Bilim V, Tasaki M, Schmitt D, Mazar A, Giles FJ, Ugolkov A, Tomita Y, Tomita Y, et al: Clinically relevant GSK‑3β inhibitor 9‑ING‑41 is active as a single agent and in combination with other antitumor therapies in human renal cancer. Int J Mol Med 45: 315-323, 2020.
APA
Anraku, T., Kuroki, H., Kazama, A., Bilim, V., Tasaki, M., Schmitt, D. ... Tomita, Y. (2020). Clinically relevant GSK‑3β inhibitor 9‑ING‑41 is active as a single agent and in combination with other antitumor therapies in human renal cancer. International Journal of Molecular Medicine, 45, 315-323. https://doi.org/10.3892/ijmm.2019.4427
MLA
Anraku, T., Kuroki, H., Kazama, A., Bilim, V., Tasaki, M., Schmitt, D., Mazar, A., Giles, F. J., Ugolkov, A., Tomita, Y."Clinically relevant GSK‑3β inhibitor 9‑ING‑41 is active as a single agent and in combination with other antitumor therapies in human renal cancer". International Journal of Molecular Medicine 45.2 (2020): 315-323.
Chicago
Anraku, T., Kuroki, H., Kazama, A., Bilim, V., Tasaki, M., Schmitt, D., Mazar, A., Giles, F. J., Ugolkov, A., Tomita, Y."Clinically relevant GSK‑3β inhibitor 9‑ING‑41 is active as a single agent and in combination with other antitumor therapies in human renal cancer". International Journal of Molecular Medicine 45, no. 2 (2020): 315-323. https://doi.org/10.3892/ijmm.2019.4427
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