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

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 concentra...

Full description

Saved in:
Bibliographic Details
Published in:Journal of natural products (Washington, D.C.) D.C.), 2016-09, Vol.79 (9), p.2304-2314
Main Authors: Grobárová, Valéria, Vališ, Karel, Talacko, Pavel, Pavlů, Barbora, Hernychová, Lucie, Nováková, Jana, Stodůlková, Eva, Flieger, Miroslav, Novák, Petr, Černý, Jan
Format: Article
Language:English
Subjects:
Antineoplastic Agents - blood
Antineoplastic Agents - chemistry
Antineoplastic Agents - isolation & purification
Antineoplastic Agents - pharmacology
Basidiomycota - chemistry
Cell Proliferation - drug effects
Drug Screening Assays, Antitumor
Humans
Jurkat Cells - drug effects
Leukocytes, Mononuclear - drug effects
Molecular Structure
Naphthoquinones - blood
Naphthoquinones - chemical synthesis
Naphthoquinones - chemistry
Naphthoquinones - isolation & purification
Naphthoquinones - pharmacology
Phosphorylation
Ribosomal Protein S6 Kinases, 70-kDa
Signal Transduction - physiology
TOR Serine-Threonine Kinases
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0163-3864
1520-6025
DOI:10.1021/acs.jnatprod.6b00362