title: Quambalarine B, a Secondary Metabolite from Quambalaria cyanescens with Potential Anticancer Properties.
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.
authors: Department of Cell Biology, Faculty of Science, Charles University , Viničná 7, 128 43 Prague 2, Czech Republic.
authors: Valéria
authors: V
authors: Grobárová
authors: Institute of Microbiology, v.v.i., The Czech Academy of Sciences , Vídeňská 1083, 142 20 Prague 4, Czech Republic.|Department of Biochemistry, Faculty of Science, Charles University , Hlavova 8, 128 43 Prague 2, Czech Republic.
authors: Karel
authors: K
authors: Vališ
authors: Institute of Microbiology, v.v.i., The Czech Academy of Sciences , Vídeňská 1083, 142 20 Prague 4, Czech Republic.|Department of Biochemistry, Faculty of Science, Charles University , Hlavova 8, 128 43 Prague 2, Czech Republic.
authors: Pavel
authors: P
authors: Talacko
authors: Department of Cell Biology, Faculty of Science, Charles University , Viničná 7, 128 43 Prague 2, Czech Republic.
authors: Barbora
authors: B
authors: Pavlů
authors: Department of Cell Biology, Faculty of Science, Charles University , Viničná 7, 128 43 Prague 2, Czech Republic.|Institute of Microbiology, v.v.i., The Czech Academy of Sciences , Vídeňská 1083, 142 20 Prague 4, Czech Republic.
authors: Lucie
authors: L
authors: Hernychová
authors: Institute of Microbiology, v.v.i., The Czech Academy of Sciences , Vídeňská 1083, 142 20 Prague 4, Czech Republic.
authors: Jana
authors: J
authors: Nováková
authors: Institute of Microbiology, v.v.i., The Czech Academy of Sciences , Vídeňská 1083, 142 20 Prague 4, Czech Republic.
authors: Eva
authors: E
authors: Stodůlková
authors: Institute of Microbiology, v.v.i., The Czech Academy of Sciences , Vídeňská 1083, 142 20 Prague 4, Czech Republic.
authors: Miroslav
authors: M
authors: Flieger
authors: Institute of Microbiology, v.v.i., The Czech Academy of Sciences , Vídeňská 1083, 142 20 Prague 4, Czech Republic.|Department of Biochemistry, Faculty of Science, Charles University , Hlavova 8, 128 43 Prague 2, Czech Republic.
authors: Petr
authors: P
authors: Novák
authors: Department of Cell Biology, Faculty of Science, Charles University , Viničná 7, 128 43 Prague 2, Czech Republic.
authors: Jan
authors: J
authors: Černý
mesh_terms: D000970:Antineoplastic Agents / Q000097:blood / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D001487:Basidiomycota / Q000737:chemistry*; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D019169:Jurkat Cells / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D015394:Molecular Structure; D009285:Naphthoquinones / Q000097:blood / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D010766:Phosphorylation; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D015398:Signal Transduction / Q000502:physiology; D058570:TOR Serine-Threonine Kinases
chemical_list: C000620742:3-hexanoyl-2,5,7,8-tetrahydroxy-1,4-naphthoquinone; D000970:Antineoplastic Agents; D009285:Naphthoquinones; C546842:MTOR protein, human; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases