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  • Title: Blockade of the interaction between Bcr-Abl and PTB1B by small molecule SBF-1 to overcome imatinib-resistance of chronic myeloid leukemia cells.
    Author: Elgehama A, Chen W, Pang J, Mi S, Li J, Guo W, Wang X, Gao J, Yu B, Shen Y, Xu Q.
    Journal: Cancer Lett; 2016 Mar 01; 372(1):82-8. PubMed ID: 26721204.
    Abstract:
    In this study, a synthetic steroidal glycoside SBF-1 had strong and preferential antitumor effects on the human chronic myeloid leukemia (CML) cell line K562 and its imatinib-resistant form K562/G. SBF-1 induced apoptosis in both cell lines without any effect on cell cycle arrest. It also inhibited the activation of PI3K/Akt pathway members, such as PI3K and Akt, as well as downstream targets mTOR and Bcl-2. Moreover, the degradation of the Bcr-Abl protein was induced by SBF-1 in a concentration- and time-dependent manner. Using a pull-down assay, SBF-1 was found to bind to both Bcr-Abl and PTP1B and disrupted the interaction between them. SBF-1 triggered the degradation of Bcr-Abl through ubiquitination via the lysosome pathway. Taking together these findings, this study, for the first time, suggests that the blockade of the interaction between Bcr-Abl and PTP1B may be a feasible strategy for the treatment of CML, especially CML with resistance to Bcr-Abl kinase inhibitor imatinib. Our study also indicates that SBF-1 may serve as a leading compound for novel anti-CML therapeutic agents.
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