Spautin-1, a novel autophagy inhibitor, enhances imatinib-induced apoptosis in chronic myeloid leukemia

  • Authors:
    • Shan Shao
    • Su Li
    • Youwen Qin
    • Xiaorui Wang
    • Yining Yang
    • Haitao Bai
    • Lili Zhou
    • Chuxian Zhao
    • Chun Wang
  • View Affiliations

  • Published online on: February 27, 2014     https://doi.org/10.3892/ijo.2014.2313
  • Pages: 1661-1668
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Abstract

Imatinib mesylate (IM), a targeted competitive inhibitor of the BCR-ABL tyrosine kinase, has revolutionized the clinical treatment of chronic myeloid leukemia (CML). However, resistance and intolerance are still a challenge in the treatment of CML. Autophagy has been proposed to play a role in IM resistance. To investigate the anti-leukemic activity of specific and potent autophagy inhibitor-1 (spautin-1) in CML, we detected its synergistic effect with IM in K562 and CML cells. Our results showed that spautin-1 markedly inhibited IM-induced autophagy in CML cells by downregulating Beclin-1. Spautin-1 enhanced IM-induced CML cell apoptosis by reducing the expression of the anti-apoptotic proteins Mcl-1 and Bcl-2. We further demonstrated that the pro-apoptotic activity of spautin-1 was associated with activation of GSK3β, an important downstream effector of PI3K/AKT. The findings indicate that the autophagy inhibitor spautin-1 enhances IM-induced apoptosis by inactivating PI3K/AKT and activating downstream GSK3β, leading to downregulation of Mcl-1 and Bcl-2, which represents a promising approach to improve the efficacy of IM in the treatment of patients with CML.
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May-2014
Volume 44 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Shao S, Li S, Qin Y, Wang X, Yang Y, Bai H, Zhou L, Zhao C and Wang C: Spautin-1, a novel autophagy inhibitor, enhances imatinib-induced apoptosis in chronic myeloid leukemia. Int J Oncol 44: 1661-1668, 2014
APA
Shao, S., Li, S., Qin, Y., Wang, X., Yang, Y., Bai, H. ... Wang, C. (2014). Spautin-1, a novel autophagy inhibitor, enhances imatinib-induced apoptosis in chronic myeloid leukemia. International Journal of Oncology, 44, 1661-1668. https://doi.org/10.3892/ijo.2014.2313
MLA
Shao, S., Li, S., Qin, Y., Wang, X., Yang, Y., Bai, H., Zhou, L., Zhao, C., Wang, C."Spautin-1, a novel autophagy inhibitor, enhances imatinib-induced apoptosis in chronic myeloid leukemia". International Journal of Oncology 44.5 (2014): 1661-1668.
Chicago
Shao, S., Li, S., Qin, Y., Wang, X., Yang, Y., Bai, H., Zhou, L., Zhao, C., Wang, C."Spautin-1, a novel autophagy inhibitor, enhances imatinib-induced apoptosis in chronic myeloid leukemia". International Journal of Oncology 44, no. 5 (2014): 1661-1668. https://doi.org/10.3892/ijo.2014.2313