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- Title
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
Anraku, Tsutomu; Kuroki, Hiroo; Kazama, Akira; Bilim, Vladimir; Tasaki, Masaaki; Schmitt, Daniel; Mazar, Andrew; Giles, Francis J.; Ugolkov, Andrey; Tomita, Yoshihiko
- 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.
- Publication
International Journal of Molecular Medicine, 2020, Vol 45, Issue 2, p315
- ISSN
1107-3756
- Publication type
Article
- DOI
10.3892/ijmm.2019.4427