Absence of genotoxic effects of the chalcone (E)-1-(2-hydroxyphenyl)-3-(4-methylphenyl)-prop-2-en-1-one) and its potential chemoprevention against DNA damage using in vitro and in vivo assays.

Débora Cristina Da Silva Lima,Aline Bernardes,Jefferson Hollanda Véras,Camila Regina Do Vale,Caridad Noda Pérez,Lee Chen-Chen,David L Mccormick

doi:10.1371/journal.pone.0171224

Débora Cristina Da Silva Lima, Aline Bernardes + Show 5 more

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https://doi.org/10.1371/journal.pone.0171224

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Journal: PloS one	Publication Date: Feb 16, 2017
Citations: 18	License type: CC BY 4.0

Affiliation: Universidade Federal de Goiás

Abstract

The chalcone (E)-1-(2-hydroxyphenyl)-3-(4-methylphenyl)-prop-2-en-1-one), or 2HMC, displays antileishmanial, antimalarial, and antioxidant activities. The aim of this study was to investigate the cytotoxic, genotoxic, mutagenic, and protective effects of 2HMC using the Ames mutagenicity test, the mouse bone marrow micronucleus test, and the comet assay in mice. In the assessment using the Ames test, 2HMC did not increase the number of His+ revertants in Salmonella typhimurium strains, demonstrating lack of mutagenicity. 2HMC showed no significant increase in micronucleated polychromatic erythrocyte frequency (MNPCE) in the micronucleus test, or in DNA strand breaks using the comet assay, evidencing absence of genotoxicity. Regarding cytotoxicity, 2HMC exhibited moderate cytotoxicity in mouse bone marrow cells by micronucleus test. 2HMC showed antimutagenic action in co-administration with the positive controls, sodium azide (SA) and 4-nitroquinoline-1-oxide (4NQO), in the Ames test. Co-administered and mainly pre-administered with cyclophosphamide (CPA), 2HMC caused a decrease in the frequency of MNPCE using the micronucleus test and in DNA strand breaks using the comet assay. Thus, 2HMC exhibited antimutagenic and antigenotoxic effects, displaying a DNA-protective effect against CPA, SA, and 4NQO carcinogens. In conclusion, 2HMC presented antimutagenic, antigenotoxic and moderate cytotoxic effects; therefore it is a promising molecule for cancer prevention.

Highlights

Chalcones (1,3-diphenyl-2-propen-1-one) are naturally occurring aromatic ketones, consisting of an α,β-unsaturated carbonyl system joining two aryl rings [1]
In Group 3, treated only with 50 mg/kg BW 2HMC (24 h), the polychromatic erythrocytes (PCE)/normochromatic erythrocytes (NCE) ratio was 0.87, while in the negative control group it was 1.1. These results demonstrate that this treatment with 2HMC caused a significant decrease in the PCE/NCE ratio compared to the negative control group (p < 0.05), suggesting a mild cytotoxic effect of the chalcone at this dose and 24 h of exposure
The results obtained in this study using the Ames test, micronucleus test, and comet assay showed that 2HMC did not exhibit mutagenic and genotoxic effects. 2HMC presented a moderate cytotoxicity in mouse bone marrow cells in micronucleus test, mainly at pre-treatment

Summary

Introduction

Chalcones (1,3-diphenyl-2-propen-1-one) are naturally occurring aromatic ketones, consisting of an α,β-unsaturated carbonyl system joining two aryl rings [1]. 2’-hydroxychalcones, known for their effectiveness in gene expression and enzyme activity [4,5], are the most important intermediates in the synthesis of flavonoids and flavones [6,7]. This group of chalcones exhibits remarkable anticancer [8] and antioxidant [9] activities, besides having potential as a neuroprotective and analgesic agent, as well as a cognitive enhancer [10]. A large variety of 2’hydroxychalcone compounds have been synthesized and studied aiming to obtain promising therapeutic agents

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