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Alternaria alternata Toxins Synergistically Activate the Aryl Hydrocarbon Receptor Pathway In Vitro.
- Source :
-
Biomolecules [Biomolecules] 2020 Jul 09; Vol. 10 (7). Date of Electronic Publication: 2020 Jul 09. - Publication Year :
- 2020
-
Abstract
- Alternaria molds simultaneously produce a large variety of mycotoxins, of which several were previously reported to induce enzymes of phase I metabolism through aryl hydrocarbon receptor activation. Thus, we investigated the potential of naturally occurring Alternaria toxin mixtures to induce Cytochrome P450 (CYP) 1A1/1A2/1B1 activity. Two variants of an extract from cultured Alternaria alternata, as well as the toxins alternariol (AOH), alternariol monomethyl ether (AME), altertoxin I (ATX-I), and altertoxin II (ATX-II), were tested singularly and in binary mixtures applying the 7-ethoxy-resorufin- O -deethylase (EROD) assay in MCF-7 breast cancer cells. Sub-cytotoxic concentrations of the two toxin mixtures, as well as ATX-I, ATX-II and AOH, exhibited dose-dependent enhancements of CYP 1 activity. ATX-I and ATX-II interacted synergistically in this respect, demonstrating the two perylene quinones as major contributors to the extract's potential. Binary mixtures between AOH and the two altertoxins respectively exhibited concentration-dependent antagonistic as well as synergistic combinatory effects. Notably, AME showed no efficacy towards EROD enzyme activity or impact on other toxins' efficacy. Hence, this study provides insights into synergistic and other combinatory effects of Alternaria toxins in natural co-occurrence scenarios in the context of AhR signalling pathway activation in breast cancer cells.
- Subjects :
- Basic Helix-Loop-Helix Transcription Factors metabolism
Benz(a)Anthracenes pharmacology
Breast Neoplasms drug therapy
Cell Proliferation drug effects
Cell Survival drug effects
Drug Synergism
Female
Gene Expression Regulation, Neoplastic drug effects
Humans
Lactones pharmacology
MCF-7 Cells
Perylene analogs & derivatives
Perylene pharmacology
Receptors, Aryl Hydrocarbon metabolism
Alternaria metabolism
Aryl Hydrocarbon Hydroxylases metabolism
Breast Neoplasms metabolism
Mycotoxins pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 2218-273X
- Volume :
- 10
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Biomolecules
- Publication Type :
- Academic Journal
- Accession number :
- 32659980
- Full Text :
- https://doi.org/10.3390/biom10071018