| Literature DB >> 27571379 |
Valéria Grobárová1, Karel Vališ2,3, Pavel Talacko2,3, Barbora Pavlů1, Lucie Hernychová1,2, Jana Nováková2, Eva Stodůlková2, Miroslav Flieger2, Petr Novák2,3, Jan Černý1.
Abstract
Quambalarine B (QB) is a secondary metabolite produced by the basidiomycete Quambalaria cyanescens with potential anticancer activity. Here we report that QB at low micromolar concentration inhibits proliferation of several model leukemic cell lines (Jurkat, NALM6, and REH), whereas higher concentrations induce cell death. By contrast, the effect of QB on primary leukocytes (peripheral blood mononuclear cells) is significantly milder with lower toxicity and cytostatic activity. Moreover, QB inhibited expression of the C-MYC oncoprotein and mRNA expression of its target genes, LDHA, PKM2, and GLS. Finally, QB blocked the phosphorylation of P70S6K, a downstream effector kinase in mTOR signaling that regulates translation of C-MYC. This observation could explain the molecular mechanism behind the antiproliferative and cytotoxic effects of QB on leukemic cells. Altogether, our results establish QB as a promising molecule in anticancer treatment.Entities:
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Year: 2016 PMID: 27571379 DOI: 10.1021/acs.jnatprod.6b00362
Source DB: PubMed Journal: J Nat Prod ISSN: 0163-3864 Impact factor: 4.050