Pregnane X receptor regulates the AhR/Cyp1A1 pathway and protects liver cells from benzo-[α]-pyrene-induced DNA damage

Cui, Hongmei; Gu, Xinsheng; Chen, Jingshu; Xie, Ying; Ke, Sui; Wu, Jing; Головко, Андрей; Morpurgo, Benjamin; Yan, Chunhong; Phillips, Timothy D.; Xie, Wen; Luo, Jianyuan; Zhou, Zhijun; Yan, Tian

doi:10.1016/j.toxlet.2017.03.028

Cited by 25 publications

(16 citation statements)

References 31 publications

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“…Probably, such a process is involved in the observed antagonism effect of PCB153 on BaP-induced luciferase expression. Moreover, it was recently described that PXR protects from BaP-induced DNA damage, and it can bound AhR at its DNA-binding domain, and this association may play a role in preventing of the AhR from binding to its target genes [ 50 ]. Inversely, concerning the expression of CYP1A1 , TNFα , and IL6 , we observed that PCB153 enhances the effect of BaP in pre-adipocytes (“Time 1” treatment).…”

Section: Discussionmentioning

confidence: 99%

In Vitro Cocktail Effects of PCB-DL (PCB118) and Bulky PCB (PCB153) with BaP on Adipogenesis and on Expression of Genes Involved in the Establishment of a Pro-Inflammatory State

May¹,

Bremond²,

Sauzet³

et al. 2018

IJMS

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(1) Objective: Highlight the in vitro effects of 3T3-L1 cell exposure to polychlorinated biphenyls (PCB118 and 153) or benzo(a)pyrene (BaP) alone or as a cocktail on adipogenesis (ADG) by focusing on changes in lipid metabolism and inflammatory-related genes expression (INFG) and ADG-related genes expression (ADGG); (2) Results: Treatment from the early stage of cell differentiation by BaP alone or in combination with PCBs decreased the expression of some of the ADGG (PPARγ Glut-4, FAS, Lipin-1a, Leptin, and Adiponectin). BaP enhanced the INFG, especially MCP-1 and TNFα. Co-exposure to BaP and PCB153 showed a synergistic effect on TNFα and IL6 expression. Treatment with BaP and PCBs during only the maturation period up-regulated the INFG (IL6, TNFα, CXCL-10 & MCP-1). PCB118 alone also enhanced TNFα, CXCL-10, and PAI-1 expression. The change in MCP-1 protein expression was in agreement with that of the gene. Finally, the BaP-induced up-regulation of the xenobiotic responsive element (XRE)-controlled luciferase activity was impaired by PCB153 but not by PCB118; (3) Conclusion: BaP and PCBs down-regulate a part of ADGG and enhance INFG. The direct regulatory effect of PCBs on both ADGG and INFG is usually rather lower than that of BaP and synergistic or antagonistic cocktail effects are clearly observed.

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Section: Discussionmentioning

confidence: 99%

In Vitro Cocktail Effects of PCB-DL (PCB118) and Bulky PCB (PCB153) with BaP on Adipogenesis and on Expression of Genes Involved in the Establishment of a Pro-Inflammatory State

May¹,

Bremond²,

Sauzet³

et al. 2018

IJMS

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“…Bolotina et al ( 35 ) demonstrated that BaP-dependent activation of transcript factors nuclear factor (NF)-κB and activator protein 1 (AP-1) was associated with tumor promotion in hepatoma cell cultures. Cui et al ( 36 ) demonstrated that pregnane X receptor regulated the AhR/CYP1A1 pathway and protected liver cells from BaP-induced DNA damage. Marrone et al ( 37 ) reported that treatment of HepaRG cells with BaP resulted in specific changes in the expression of microRNAs compared with their non-carcinogenic analogues.…”

Section: Discussionmentioning

confidence: 99%

Benzo(a)pyrene promotes Hep‑G2 cell migration and invasion by upregulating phosphorylated extracellular signal‑regulated kinase expression

Wang

Pan

et al. 2018

Oncol Lett

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Benzo(a)pyrene (BaP), a carcinogenic component of cigarette smoke, has been reported to activate extracellular signal-regulated kinase (ERK) in cancer cells. Furthermore, activated ERK is associated with liver cancer cell invasion and metastasis. Therefore, the aim of the present study was to investigate the potential role of phosphorylated (p)-ERK in BaP-induced Hep-G2 cell migration and invasion. An MTT assay was used to determine the effects of BaP treatment on Hep-G2 cell proliferation. Wound-healing and Transwell invasion assays were employed to assess the migration and invasion abilities of Hep-G2 cells. Western blot analysis was applied to detect the expression of proteins. The results of the present study demonstrated that BaP treatment was able to increase the level of p-ERK protein expression in Hep-G2 cells. BaP treatment promoted Hep-G2 cell migration and invasion. The ERK inhibitor, U0126, was able to block the migration and invasion abilities of Hep-G2 cells induced by BaP. The results of the present study demonstrated that BaP treatment promoted the migration and invasion of Hep-G2 cells by upregulating p-ERK expression.

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“…Silica was listed as a human carcinogen by IARC in 1997. B(a)P was a former carcinogen that required metabolic activation to form the final activated substance, which has also been listed as a human carcinogen by IARC (Park et al, 2015;Cui et al, 2017). But now, the carcinogenic mechanisms of silica and B(a)P are unclear.…”

Section: Activation Of Mapk and Cyclin D1/cdk4 In Malignant Transformmentioning

confidence: 99%

Activation of MAPK and Cyclin D1/CDK4 in Malignant Transformation of Human Embryonic Lung Fibroblasts Induced by Silica and Benzopyrene

Wang

Xiao²,

Tang

et al. 2020

Asian Pac J Cancer Prev

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Objective: Silica and Benzo(a)pyrene are listed as carcinogens. This study aims to explore Cyclin D1, CDK4 and difference of cell cycle adjusted by MAPK signal transduction pathway in silica and B(a)P-induced malignant transformation of human embryonic lung fibroblasts. Methods: Activity of the subfamily (ERK, p38 and JNK) of mitogen-activated protein kinase (MAPK), cyclin D1 and CDK4 (cyclin dependent kinase) were evaluated using Human embryonic lung fibroblast (HELF) purchased from the cell room, basic research institute, Chinese Academy of Medical Sciences. The expression of cyclin D1 and CDK4 (cyclin dependent kinase) were measured in silica and B(a) P induced malignant using Western blot (WB) assay. Results: PERK and P-JNK expression increased significantly (P<0.01), while CDK4 and P-p38 expression decreased (P<0.01, P<0.05) in silica-induced malignant transformation cells compared with the control group. PERK , P-JNK and Cyclin D1 expression increased (P<0.01, P<0.01, P<0.05) in B(a)P-induced group compared with the control group. PERK and P-JNK expression decreased (P<0.01), while P-p38, Cyclin D1 and CDK4 expression increased (P<0.05, P<0.05, P<0.01) in B(a)P-induced group compared with the silica-induced group. Conclusion: MAPK and cyclin D1/CDK4 activation expressed differently in human embryo lung fibroblasts malignant transformation induced by silica and benzopyrene.

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Pregnane X receptor regulates the AhR/Cyp1A1 pathway and protects liver cells from benzo-[α]-pyrene-induced DNA damage

Cited by 25 publications

References 31 publications

In Vitro Cocktail Effects of PCB-DL (PCB118) and Bulky PCB (PCB153) with BaP on Adipogenesis and on Expression of Genes Involved in the Establishment of a Pro-Inflammatory State

In Vitro Cocktail Effects of PCB-DL (PCB118) and Bulky PCB (PCB153) with BaP on Adipogenesis and on Expression of Genes Involved in the Establishment of a Pro-Inflammatory State

Benzo(a)pyrene promotes Hep‑G2 cell migration and invasion by upregulating phosphorylated extracellular signal‑regulated kinase expression

Activation of MAPK and Cyclin D1/CDK4 in Malignant Transformation of Human Embryonic Lung Fibroblasts Induced by Silica and Benzopyrene

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