Synephrine and caffeine combination promotes cytotoxicity, DNA damage and transcriptional modulation of apoptosis-related genes in human HepG2 cells

•This study examined toxicogenomic effects of Synephrine (SN) and Caffeine (CAF).•SN/CAF combination induced cytotoxicity, cell death, and DNA damage in HepG2 cells.•Apoptosis (BCL-2/CASP9) and DNA repair (XPC) genes were up-regulated.•Downregulation of cell cycle CDKN1A gene expression was associat...

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Published in:	Mutation research. Genetic toxicology and environmental mutagenesis Vol. 868-869; p. 503375
Main Authors:	Leão, Tainá Keiller, Ribeiro, Diego Luís, Machado, Ana Rita Thomazela, Costa, Tássia Rafaela, Sampaio, Suely Vilela, Antunes, Lusânia Maria Greggi
Format:	Journal Article
Language:	English
Published:	Elsevier B.V 01-08-2021
Subjects:	Comet assay Cytotoxicity Gene expression HepG2 cells Nutrigenomic Cytotoxicity HepG2 cells Nutrigenomic Gene expression Comet assay
Online Access:	Get full text
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Summary:	•This study examined toxicogenomic effects of Synephrine (SN) and Caffeine (CAF).•SN/CAF combination induced cytotoxicity, cell death, and DNA damage in HepG2 cells.•Apoptosis (BCL-2/CASP9) and DNA repair (XPC) genes were up-regulated.•Downregulation of cell cycle CDKN1A gene expression was associated with apoptosis.•These harmful effects can be worrisome to consumers of thermogenic supplements. The abusive consumption of thermogenic supplements occurs worldwide and deserves special attention due to their use to stimulate weight loss and prevent obesity. Thermogenic formulations usually contain Synephrine (SN) and Caffeine (CAF), stimulating compounds extracted from natural sources, but no genetic toxicology studies have predicted this hazardous combination potential. This study examined the toxicogenomic responses induced by SN and CAF, either alone or in combination, in the human hepatic cell line HepG2 in vitro. SN (0.03–30 μM) and CAF (0.6–600 μM) alone did neither decrease cell viability nor induce DNA damage, as assessed using the MTT and comet assays, respectively. SN (3 μM) and CAF (30–600 μM) were combined at concentrations similar to those found in commercial dietary supplements. SN/CAF at 3:90 and 3:600 μM ratios significantly decreased cell viability and increased DNA damage levels in HepG2 cells. CAF (600 μM) and the SN/CAF association at 3:60, 3:90, and 3:600 μM ratios promoted cell death by apoptosis, as demonstrated by flow cytometry. Similar results were observed in gene expression (RT-qPCR): SN/CAF up-regulated the expression of apoptosis- (BCL-2 and CASP9) and DNA repair-related (XPC) genes. SN/CAF at 3:90 μM also downregulated the expression of cell cycle control (CDKN1A) genes. In conclusion, the SN/CAF combination reduces cell viability by inducing apoptosis, damages DNA, and modulates the transcriptional expression of apoptosis-, cell cycle-, and DNA repair-related genes in human hepatic (HepG2) cells in vitro. These effects can be worrisome to consumers of thermogenic supplements.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1383-5718 1879-3592
DOI:	10.1016/j.mrgentox.2021.503375