The Garlic Compound, Diallyl Trisulfide, Attenuates Benzo[a]Pyrene-Induced Precancerous Effect through Its Antioxidant Effect, AhR Inhibition, and Increased DNA Repair in Human Breast Epithelial Cells
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Published:2024-01-19
Issue:2
Volume:16
Page:300
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ISSN:2072-6643
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Container-title:Nutrients
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language:en
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Short-container-title:Nutrients
Author:
Ferguson Dominique T.1ORCID, Taka Equar1, Messeha Samia1, Flores-Rozas Hernan1, Reed Sarah L.1, Redmond Bryan V.2ORCID, Soliman Karam F. A.1ORCID, Kanga Konan J. W.3, Darling-Reed Selina F.1
Affiliation:
1. Pharmaceutical Sciences Division, College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA 2. Department of Neuroscience, University of Rochester Medical Center, Rochester, NY 14642, USA 3. Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, FL 32306, USA
Abstract
Exposure to B[a]P, the most characterized polycyclic aromatic hydrocarbon, significantly increases breast cancer risk. Our lab has previously reported that diallyl trisulfide (DATS), a garlic organosulfur compound (OSC) with chemopreventive and cell cycle arrest properties, reduces lipid peroxides and DNA damage in normal breast epithelial (MCF-10A) cells. In this study, we evaluated the ability of DATS to block the B[a]P-induced initiation of carcinogenesis in MCF-10A cells by examining changes in proliferation, clonogenic formation, reactive oxygen species (ROS) formation, 8-hydroxy-2-deoxyguanosine (8-OHdG) levels, and protein expression of ARNT/HIF-1β, CYP1A1, and DNA POLβ. The study results indicate that B[a]P increased proliferation, clonogenic formation, ROS formation, and 8-OHdG levels, as well as increasing the protein expression of ARNT/HIF-1β and CYP1A1 compared to the control. Conversely, DATS/B[a]P co-treatment (CoTx) inhibited cell proliferation, clonogenic formation, ROS formation, and 8-OHdG levels compared to B[a]P alone. Treatment with DATS significantly inhibited (p < 0.0001) AhR expression, implicated in the development and progression of breast cancer. The CoTx also attenuated all the above-mentioned B[a]P-induced changes in protein expression. At the same time, it increased DNA POLβ protein expression, which indicates increased DNA repair, thus causing a chemopreventive effect. These results provide evidence for the chemopreventive effects of DATS in breast cancer prevention.
Funder
National Institute on Minority Health and Health Disparities
Subject
Food Science,Nutrition and Dietetics
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