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Jangam Reddy, J.R. and Panigrahi, S. and Lotfi, K. and Yadav, M. and Subba Reddy, Maddika and Tripathi, A.K. and Sanyal, S. and Łos, M.J. (2014) Mapping of apoptin-interaction with BCR-ABL1, and development of apoptin-based targeted therapy. Oncotarget, 5 (16). pp. 7198-7211. ISSN 1949-2553
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Oncotarget 5 p7198 2014 Aug.pdf - Published Version Available under License Creative Commons Attribution. Download (2054Kb) | Preview |
Abstract
Majority of chronic myeloid leukemia patients experience an adequate therapeutic effect from imatinib however, 26-37% of patients discontinue imatinib therapy due to a suboptimal response or intolerance. Here we investigated derivatives of apoptin, a chicken anemia viral protein with selective toxicity towards cancer cells, which can be directed towards inhibiting multiple hyperactive kinases including BCR-ABL1. Our earlier studies revealed that a proline-rich segment of apoptin interacts with the SH3 domain of fusion protein BCR-ABL1 (p210) and acts as a negative regulator of BCR-ABL1 kinase and its downstream targets. In this study we show for the first time, the therapeutic potential of apoptin-derived decapeptide for the treatment of CML by establishing the minimal region of apoptin interaction domain with BCR-ABL1. We further show that the apoptin decapeptide is able to inhibit BCR-ABL1 down stream target c-Myc with a comparable efficacy to full-length apoptin and Imatinib. The synthetic apoptin is able to inhibit cell proliferation in murine (32Dp210), human cell line (K562), and ex vivo in both imatinib-resistant and imatinib sensitive CML patient samples. The apoptin based single or combination therapy may be an additional option in CML treatment and eventually be feasible as curative therapy
| Item Type: | Article |
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| Uncontrolled Keywords: | apoptin, BCR-ABL1, CML, imatinib, STAT5 |
| Subjects: | Cell Biology Molecular Biology |
| Depositing User: | Users 2 not found. |
| Date Deposited: | 17 May 2015 19:42 |
| Last Modified: | 21 Sep 2015 05:48 |
| URI: | http://cdfd.sciencecentral.in/id/eprint/47 |
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