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国际药用蘑菇期刊
影响因子: 1.423 5年影响因子: 1.525 SJR: 0.431 SNIP: 0.716 CiteScore™: 2.6

ISSN 打印: 1521-9437
ISSN 在线: 1940-4344

国际药用蘑菇期刊

DOI: 10.1615/InterJMedicMush.v5.i3.40
16 pages

Submerged Cultured Mycelium Extracts of Higher Basidiomycetes Mushrooms Selectively Inhibit Proliferation and Induce Differentiation of K562 Human Chronic Myelogenous Leukemia Cells

Majed Yassin
Institute of Evolution, University of Haifa, Mount Carmel, Haifa, Israel; Migal, Galilee Technology Center, Kiryat Shmona, Israel; Galilee Institute for Applied Research, Nazareth, Israel
Jamal A. Mahajna
Migal, Galilee Technology Center, Cancer Drug Discovery Program, Kiryat Shmona; Galilee Institute for Applied Research, Nazareth

ABSTRACT

Human chronic myelogenous leukemia (CML) is a malignancy of pluripotent hematopoietic cells characterized by a distinctive cytogenetic abnormality known as the Philadelphia (Ph) chromosome, which results in the creation of a p210Bcr–Abl fusion protein with increased tyrosine kinase activity. Forty-two species of Higher Basidiomycetes mushrooms were cultivated as pure cultures in submerged conditions, and dry mycelium was used to prepare 168 different crude extracts. The crude extracts were used to evaluate antiproliferative activity against a number of cancer cell lines, including K562 (human chronic myelogenous leukemia cell line), Jurkat (human T lymphoblast cells), HT29 (human colon adenocarcinoma cells), MH3924A (rat Morris hepatoma), and ABAE (adult bovine aortic endothelial cells) using XTT proliferation assay. Forty-four crude extracts with antiproliferative effect against K562 cells were selected, and eight mycelium extracts were K562-selective compared with MH3924A, HT29, ABAE, and Jurkat cells. Growth inhibition against K562 ranged from 51% to 78% compared with solvent-treated samples. Most crude extracts exhibited a complete or partial cytostatic effect against K562 cells. The anti-proliferative effect observed by the selected crude extracts was attributed to the induction of an apoptosis pathway as determined by Apostain ELISA assay and by monitoring PARP cleavage. It is interesting that crude extract MH428 was the most active extract in inducing apoptosis of K562 cells. In addition, expression levels of p210Bcr–Abl were affected by the presence of the selected crude extracts. Our data revealed a significant inhibition of p210Bcr–Abl expression by MH428 extract, a moderate effect by MH17, and minor changes by the other extracts. Furthermore, mycelium crude extracts were active in inducing erythroid differentiation in K562 cells. Crude extracts Meth178, MH17, and MH428 showed significant ability to induce hemoglobin production in K562 cells, as indicative of erythroid differentiation. The results obtained support the potential use of the crude mycelium extracts for the treatment of CML and beta-globin disorders.


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