Quambalarine B, a Secondary Metabolite from Quambalaria cyanescens with Potential Anticancer Properties

0465227 - MBÚ 2017 RIV US eng J - Článek v odborném periodiku
Grobárová, V. - Vališ, Karel - Talacko, Pavel - Pavlů, B. - Hernychová, Lucie - Nováková, Jana - Stodůlková, Eva - Flieger, Miroslav - Novák, Petr - Černý, J.
Quambalarine B, a Secondary Metabolite from Quambalaria cyanescens with Potential Anticancer Properties.
Journal of Natural Products. Roč. 79, č. 9 (2016), s. 2304-2314. ISSN 0163-3864. E-ISSN 1520-6025
Grant CEP: GA MŠMT(CZ) ED1.1.00/02.0109; GA ČR GA13-16565S; GA ČR(CZ) GP14-21095P
Institucionální podpora: RVO:61388971
Klíčová slova: C-MYC * ENERGY-METABOLISM * NATURAL-PRODUCTS
Kód oboru RIV: EE - Mikrobiologie, virologie
Impakt faktor: 3.281, rok: 2016

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.
Trvalý link: http://hdl.handle.net/11104/0264319