Substances from the medicinal mushroom Daedalea gibbosa inhibit kinase activity of native and T315I mutated Bcr-Abl

  • Authors:
    • Majed Yassin
    • Solomon P. Wasser
    • Jamal Mahajna
  • View Affiliations

  • Published online on: June 1, 2008     https://doi.org/10.3892/ijo.32.6.1197
  • Pages: 1197-1204
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Abstract

Human chronic myelogenous leukemia (CML) is a malignancy of pluripotent hematopoietic cells characterized by a distinctive cytogenetic abnormality resulting in the creation of a p210 Bcr-Abl fusion protein with abnormal tyrosine kinase activity. Recently, a selective Abl kinase inhibitor, Imatinib mesylate, was introduced as a first line therapy for CML. Despite the initial response, CML patients develop a resistantance to Imatinib, which is mediated mainly by point mutations within the Abl protein. Herein, we describe the identification of mycelium organic extracts of Daedalea gibbosa with selective anti-proliferating and apoptosis-inducing activities against K562 cells and other laboratory model of CML. Using activity-guided purification, we isolated an active fraction, F6, which inhibits in vitro kinase activity of recombinant Abl. The active fraction significantly inhibits the autophosphorylation of native and mutated Bcr-Abl, which are resistant to Imatinib treatment including the T315I mutation. Using a colony-forming assay, we demon-strated that the active fraction is effective in inhibiting the colony formation of the Ba/F3 cell line harboring either native Bcr-Abl or its mutations, including the T315I mutation. Our data illustrated the potential of natural products in cancer therapeutics.

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June 2008
Volume 32 Issue 6

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

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Spandidos Publications style
Yassin M, Wasser SP and Mahajna J: Substances from the medicinal mushroom Daedalea gibbosa inhibit kinase activity of native and T315I mutated Bcr-Abl. Int J Oncol 32: 1197-1204, 2008.
APA
Yassin, M., Wasser, S.P., & Mahajna, J. (2008). Substances from the medicinal mushroom Daedalea gibbosa inhibit kinase activity of native and T315I mutated Bcr-Abl. International Journal of Oncology, 32, 1197-1204. https://doi.org/10.3892/ijo.32.6.1197
MLA
Yassin, M., Wasser, S. P., Mahajna, J."Substances from the medicinal mushroom Daedalea gibbosa inhibit kinase activity of native and T315I mutated Bcr-Abl". International Journal of Oncology 32.6 (2008): 1197-1204.
Chicago
Yassin, M., Wasser, S. P., Mahajna, J."Substances from the medicinal mushroom Daedalea gibbosa inhibit kinase activity of native and T315I mutated Bcr-Abl". International Journal of Oncology 32, no. 6 (2008): 1197-1204. https://doi.org/10.3892/ijo.32.6.1197