Angiogenesis signaling in breast cancer models is induced by hexachlorobenzene and chlorpyrifos, pesticide ligands of the aryl hydrocarbon receptor

Zárate, Lorena Vanesa; Pontillo, Carolina; Español, Alejandro; Miret, Noelia; Chiappini, Florencia; Cocca, Claudia; Álvarez, Laura; Pisarev, Diana Kleiman de; Sales, Marı́a Elena; Randi, Andrea

doi:10.1016/j.taap.2020.115093

Cited by 23 publications

(11 citation statements)

References 64 publications

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“…AhR was reported to regulate COX2 expression and PGE2 levels . CPF was reported to induce COX2 expression in MCF-7 cells through AhR and to increase PGE2 levels after single treatment, which supports our data.…”

supporting

confidence: 91%

Aryl Hydrocarbon Receptor Activation Produces Heat Shock Protein 90 and 70 Overexpression, Prostaglandin E2/Wnt/β-Catenin Signaling Disruption, and Cell Proliferation in MCF-7 and MDA-MB-231 Cells after 24 h and 14 Days of Chlorpyrifos Treatment

García

Moyano

Pelayo

et al. 2021

Chem. Res. Toxicol.

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The biocide chlorpyrifos (CPF) was described to increase breast cancer risk in humans, to produce breast cancer in animals, and to induce cell proliferation in MCF-7 and MDA-MB-231 cells after 1 and 14 days of treatment. The entire mechanisms related to these CPF actions remain unknown. CPF induced cell proliferation in MCF-7 and MDA-MB-231 cells after 1 and 14 days of treatment by AhR activation through the PGE2/Wnt/β-catenin pathway and HSP90 and HSP70 overexpression. Our results reveal new information on CPF toxic mechanisms induced in human breast cancer cell lines, which could assist in elucidating its involvement in breast cancer.

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supporting

confidence: 91%

Aryl Hydrocarbon Receptor Activation Produces Heat Shock Protein 90 and 70 Overexpression, Prostaglandin E2/Wnt/β-Catenin Signaling Disruption, and Cell Proliferation in MCF-7 and MDA-MB-231 Cells after 24 h and 14 Days of Chlorpyrifos Treatment

García

Moyano

Pelayo

et al. 2021

Chem. Res. Toxicol.

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“…In spite of these facts, pesticidal toxicity in the ECs and their effects on angiogenesis is sparse. Notwithstanding with the fact, MCF‐7 xenograft animal model exposed to chlorpyrifos and hexachlorobenzene exhibited tubulogenesis in the ECs, which may promote angiogenesis, a process contributing in breast cancer progression (Zárate et al, 2020). Transgenic zebra fishes exposed to herbicide (picolinafen) exhibited less blood vessel formation around the trunk region (Lee et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Cytotoxicity and genotoxicity of methomyl, carbaryl, metalaxyl, and pendimethalin in human umbilical vein endothelial cells

Saquib

Siddiqui

Ansari

et al. 2021

J of Applied Toxicology

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Pesticides have adverse effects on the cellular functionality, which may trigger myriad of health consequences. However, pesticides‐mediated toxicity in the endothelial cells (ECs) is still elusive. Hence, in this study, we have used human umbilical vein endothelial cells (HUVECs) as a model to quantify the cytotoxicity and genotoxicity of four pesticides (methomyl, carbaryl, metalaxyl, and pendimethalin). In the MTT assay, HUVECs exposed to methomyl, carbaryl, metalaxyl, and pendimethalin demonstrated significant proliferation inhibition only at higher concentrations (500 and 1000 μM). Likewise, neutral red uptake (NRU) assay also showed proliferation inhibition of HUVECs at 500 and 1000 μM by the four pesticides, confirming lysosomal fragility. HUVECs exposed to the four pesticides significantly increased the level of intracellular reactive oxygen species (ROS). Comet assay and flow cytometric data exhibited DNA damage and apoptotic cell death in HUVECs after 24 h of exposure with methomyl, metalaxyl, carbaryl, and pendimethalin. This is a first study on HUVECs signifying the cytotoxic–genotoxic and apoptotic potential of carbamate insecticides (methomyl and carbaryl), fungicide (metalaxyl), and herbicide (pendimethalin). Overall, these pesticides may affect ECs functions and angiogenesis; nonetheless, mechanistic studies are warranted from the perspective of vascular biology using in vivo test models.

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“…However, in the present work, genotoxicity was not related to the malignant transformation observed after acute or long-term exposure to the contaminants, as supported by the PCA analysis. Therefore, we investigated non-genomic carcinogenic effects, which are known to disrupt different signalling pathways [57,58].…”

Section: Discussionmentioning

confidence: 99%

Short-Term and Long-Term Carcinogenic Effects of Food Contaminants (4-Hydroxynonenal and Pesticides) on Colorectal Human Cells: Involvement of Genotoxic and Non-Genomic Mechanisms

Arnaud

Gauthier

Naour

et al. 2021

Cancers

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To investigate environmental impacts upon colorectal carcinogenesis (CRC) by diet, we assessed two western diet food contaminants: 4-hydroxynonenal (HNE), a major lipid peroxidation product neoformed during digestion, and a mixture of pesticides. We used human colonic cell lines ectopically eliciting varied genetic susceptibilities to CRC: the non-transformed human epithelial colonic cells (HCECs) and their five isogenic cell lines with the loss of APC (Adenomatous polyposis coli) and TP53 (Tumor protein 53) and/or ectopic expression of mutated KRAS (Kristen-ras). These cell lines have been exposed for either for a short time (2 -24 h) or for a long period (3 weeks) to 1 µM HNE and/or 10 µM pesticides. After acute exposure, we did not observe any cytotoxicity or major DNA damage. However, long-term exposure to pesticides alone and in mixture with HNE induced clonogenic transformation in normal HCECs, as well as in cells representing later stages of carcinogenesis. It was associated with genotoxic and non-genomic mechanisms (cell growth, metabolic reprogramming, cell mobility and epithelial-mesenchymal transition) depending on genetic susceptibility. This study demonstrated a potential initiating and promoting effect of food contaminants on CRC after long-term exposure. It supports that these contaminants can accelerate carcinogenesis when mutations in oncogenes or tumor suppressor genes occur.

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Angiogenesis signaling in breast cancer models is induced by hexachlorobenzene and chlorpyrifos, pesticide ligands of the aryl hydrocarbon receptor

Cited by 23 publications

References 64 publications

Aryl Hydrocarbon Receptor Activation Produces Heat Shock Protein 90 and 70 Overexpression, Prostaglandin E2/Wnt/β-Catenin Signaling Disruption, and Cell Proliferation in MCF-7 and MDA-MB-231 Cells after 24 h and 14 Days of Chlorpyrifos Treatment

Aryl Hydrocarbon Receptor Activation Produces Heat Shock Protein 90 and 70 Overexpression, Prostaglandin E2/Wnt/β-Catenin Signaling Disruption, and Cell Proliferation in MCF-7 and MDA-MB-231 Cells after 24 h and 14 Days of Chlorpyrifos Treatment

Cytotoxicity and genotoxicity of methomyl, carbaryl, metalaxyl, and pendimethalin in human umbilical vein endothelial cells

Short-Term and Long-Term Carcinogenic Effects of Food Contaminants (4-Hydroxynonenal and Pesticides) on Colorectal Human Cells: Involvement of Genotoxic and Non-Genomic Mechanisms

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