Benzo(a)pyrene-induced cytotoxicity, cell proliferation, DNA damage, and altered gene expression profiles in HT-29 human colon cancer cells

Myers, Jeremy N.; Harris, Kelly L.; Rekhadevi, Perumalla V.; Pratap, Siddharth; Ramesh, Aramandla

doi:10.1007/s10565-020-09579-5

Cited by 25 publications

(15 citation statements)

References 72 publications

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“…These results are consistent with other studies. Thus, upon treatment of HT-29 cells with 25 μM BaP, the number of cells in the S-phase increased, concomitantly with a decline in the number of cells in the G1 phase ( 28 ). When administrated together with BaP, eriodictyol and naringenin at least partly counteracted the changes of the cell cycle caused by BaP.…”

Section: Resultsmentioning

confidence: 99%

Proteomic Analysis of the Protective Effect of Eriodictyol on Benzo(a)pyrene-Induced Caco-2 Cytotoxicity

et al. 2022

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We evaluated the possible protective effects of six polyphenols on benzo(a)pyrene (BaP)-induced cytotoxicity in Caco-2 cells. We show that treatment with quinic acid, ferulic acid, homovanillic acid, trolox and BaP decreased cell viability, whereas naringenin and eriodictyol affected viability in a bi-phasic manner with low concentrations decreasing viability whereas higher concentrations increase viability. Co-treatment with 20 μM eriodictyol or naringenin reduced BaP-induced cytotoxicity, including cell apoptosis, cell cycle progression, and oxidative stress. Our results show that the protective effect of eriodictyol was superior to that of naringenin. The potential protective mechanisms of eriodictyol on BaP-induced toxicity were investigated by proteomics. We identified 80 differentially expressed proteins (DEPs) with proteins associated with genetic information processing pathway representing the highest proportion and number of proteins responding to eriodictyol treatment, including key proteins such as RPA2, SNRPA, RAD23B, NUP155 and AARS. Our results provide new knowledge on how polyphenols may prevent BaP-induced carcinogenesis.

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Section: Resultsmentioning

confidence: 99%

Proteomic Analysis of the Protective Effect of Eriodictyol on Benzo(a)pyrene-Induced Caco-2 Cytotoxicity

et al. 2022

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“…The toxicity of B[a]P towards primary human colonic epithelial cells (HCoEpC) was first investigated. Indeed, although previous papers showed that this compound is cytotoxic to several cancer cell lines, primary cells [ 24 , 25 ] and in mouse model [ 26 ], no in vitro studies on primary human colonic epithelial cells have been performed yet.…”

Section: Resultsmentioning

confidence: 99%

“…Benzo[a]pyrene (B[a]P) is a common environmental and food contaminant, whose increased concentration in food is linked to the cooking methods [ 38 ]. B[a]P is thought to be involved in colon carcinogenesis [ 39 ] and in this study, for the first time, we exposed primary human colonic epithelial cells (HCoEpC) to a B[a]P concentration falling in the assumption range through diet [ 24 ]. According to previously reported in vitro [ 24 , 25 ] and in vivo studies [ 26 ], we observed a partial cytotoxic effect of this molecule that correlated with a reduction in p21 in HCoEpC, as p21 inhibitor UC2288 lowered HCoEpC cell viability.…”

Section: Discussionmentioning

confidence: 99%

“…B[a]P is thought to be involved in colon carcinogenesis [ 39 ] and in this study, for the first time, we exposed primary human colonic epithelial cells (HCoEpC) to a B[a]P concentration falling in the assumption range through diet [ 24 ]. According to previously reported in vitro [ 24 , 25 ] and in vivo studies [ 26 ], we observed a partial cytotoxic effect of this molecule that correlated with a reduction in p21 in HCoEpC, as p21 inhibitor UC2288 lowered HCoEpC cell viability. The reduction in p21 detected in HCoEpC treated by B[a]P could be due to a post-translational regulation; indeed, B[a]P belongs to polycyclic aromatic hydrocarbon carcinogens (PAHs) that have been demonstrated to promote p21-ubiqutination and proteasomal degradation in other cell types [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

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3,4-Dihydroxyphenylethanol (DPE or Hydroxytyrosol) Counteracts ERK1/2 and mTOR Activation, Pro-Inflammatory Cytokine Release, Autophagy and Mitophagy Reduction Mediated by Benzo[a]pyrene in Primary Human Colonic Epithelial Cells

et al. 2022

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Understanding the effects induced by carcinogens on primary colonic epithelial cells and how to counteract them might help to prevent colon cancer, which is one of the most frequent and aggressive cancers. In this study, we exposed primary human colonic epithelial cells (HCoEpC) to Benzo[a]pyrene (B[a]P) and found that it led to an increased production of pro-inflammatory cytokines and activated ERK1/2 and mTOR. These pathways are known to be involved in inflammatory bowel disease (IBD), which represents a colon cancer risk factor. Moreover, B[a]P reduced autophagy and mitophagy, processes whose dysregulation has been clearly demonstrated to predispose to cancer either by in vitro or in vivo studies. Interestingly, all the effects induced by B[a]P could be counteracted by 3,4-Dihydroxyphenylethanol (DPE or Hydroxytyrosol, H), the most powerful anti-inflammatory and antioxidant compound contained in olive oil. This study sheds light on the mechanisms that could be involved in colon carcinogenesis induced by a chemical carcinogen and identifies a safe natural product that may help to prevent them.

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“…Hep-G2 cells have low gene expression levels of cytochrome CYP450 enzymes and xenobiotic receptors; however, they are well-known hepatic cell lines that are easy to handle and cost-effective [ 43 , 44 ]. In addition, HT-29 cells are commonly used as a human intestinal function model in vitro to study cell toxicity [ 45 , 46 ]. The imbalance between ROS generation and the antioxidant activity of the cells promotes the oxidative stress responsible for cell damage and apoptosis [ 47 ].…”

Section: Resultsmentioning

confidence: 99%

Evaluation of Toxicity and Oxidative Stress of 2-Acetylpyridine-N(4)-orthochlorophenyl Thiosemicarbazone

Lira

Parrilha

Dias

et al. 2022

Oxidative Medicine and Cellular Longevity

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Thiosemicarbazones are well known for their broad spectrum of action, including antitumoral and antiparasitic activities. Thiosemicarbazones work as chelating binders, reacting with metal ions. The objective of this work was to investigate the in silico, in vitro, and in vivo toxicity and oxidative stress of 2-acetylpyridine-N(4)-orthochlorophenyl thiosemicarbazone (TSC01). The in silico prediction showed good absorption by biological membranes and no theoretical toxicity. Also, the compound did not show cytotoxicity against Hep-G2 and HT-29 cells. In the acute nonclinical toxicological test, the animals treated with TSC01 showed behavioral changes of stimulus of the central nervous system (CNS) at 300 mg/kg. One hour after administration, a dose of 2000 mg/kg caused depressive signs. All changes disappeared after 24 h, with no deaths, which suggest an estimated LD50 of 5000 mg/kg and GSH 5. The group treated with 2000 mg/kg had an increase of water consumption and weight gain in the second week. The biochemical parameters presented no toxicity relevance, and the analysis of oxidative stress in the liver found an increase of lipid peroxidation and nitric oxide. However, histopathological analysis showed organ integrity was maintained without any changes. In conclusion, the results show the low toxicological potential of thiosemicarbazone derivative, indicating future safe use.

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Benzo(a)pyrene-induced cytotoxicity, cell proliferation, DNA damage, and altered gene expression profiles in HT-29 human colon cancer cells

Cited by 25 publications

References 72 publications

Proteomic Analysis of the Protective Effect of Eriodictyol on Benzo(a)pyrene-Induced Caco-2 Cytotoxicity

Proteomic Analysis of the Protective Effect of Eriodictyol on Benzo(a)pyrene-Induced Caco-2 Cytotoxicity

3,4-Dihydroxyphenylethanol (DPE or Hydroxytyrosol) Counteracts ERK1/2 and mTOR Activation, Pro-Inflammatory Cytokine Release, Autophagy and Mitophagy Reduction Mediated by Benzo[a]pyrene in Primary Human Colonic Epithelial Cells

Evaluation of Toxicity and Oxidative Stress of 2-Acetylpyridine-N(4)-orthochlorophenyl Thiosemicarbazone

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