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

Abstract

Human Chronic Myelogenous Leukemia (CML) is a malignancy of pluripotent hematopoietic cells characterized by distinctive cytogenetic abnormality known as the Philadelphia (Ph) chromosome, which resulted in the creation of a p210 Bcr-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 were used to prepare 168 different crude extracts. The crude extracts were used to evaluate anti-proliferative 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 different crude extracts were selected with anti-proliferative effect against K562 cells and eight mycelium extracts were K562selective 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 apoptosis pathway as determined by Apostain ELISA assay and by monitoring PARP cleavage. Interestingly, crude extract MH428 was the most active extract in inducing apoptosis of K562 cells. In addition, expression levels of p210 Bcr-Abl were affected by the presence of the selected crude extracts. Our data revealed a significant inhibition of p210 Bcr-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 show 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.