2022 Volume 17 Issue 5
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Li Siqi, Xu Tong, Xu Li, Chen Yangsheng, Zheng Liping, Xie Qunhui, Zhao Bin. Cross-talk of Bromocarbazoles between Estrogen Receptor Pathway and Aryl Hydrocarbon Receptor Pathway in Human Breast Cancer Cells (MCF-7 Cells)[J]. Asian journal of ecotoxicology, 2022, 17(5): 13-23. doi: 10.7524/AJE.1673-5897.20220314002
Citation: Li Siqi, Xu Tong, Xu Li, Chen Yangsheng, Zheng Liping, Xie Qunhui, Zhao Bin. Cross-talk of Bromocarbazoles between Estrogen Receptor Pathway and Aryl Hydrocarbon Receptor Pathway in Human Breast Cancer Cells (MCF-7 Cells)[J]. Asian journal of ecotoxicology, 2022, 17(5): 13-23. doi: 10.7524/AJE.1673-5897.20220314002
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Cross-talk of Bromocarbazoles between Estrogen Receptor Pathway and Aryl Hydrocarbon Receptor Pathway in Human Breast Cancer Cells (MCF-7 Cells)

  • 1. State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China;

  • 2. Sino-Danish College, University of Chinese Academy of Sciences, Beijing 100049, China;

  • 3. Nanjing Institute of Environmental Sciences, Ministry of Ecology and Environment of China, Nanjing 210042, China;

  • 4. State Environmental Protection Key Laboratory of Soil Environmental Management and Pollution Control, Nanjing 210042, China

  • Polyhalogenated carbazoles are heterocyclic aromatic hydrocarbon compounds with a similar structure to dioxins, which have been detected in environments and organisms. Among them, bromocarbazoles (BCZs) present strong persistence and bioaccumulation potential, and have shown dioxin-like toxicity and endocrine disrupting effects in different organisms, posing potential risks to human health. Studies have shown that BCZs can activate aryl hydrocarbon receptor (AhR) and estrogen receptor (ER) in different types of cells. The ER and AhR pathway are closely related to the occurrence and development of breast cancer. However, the interactions between the ER and AhR pathways induced by BCZs in human breast cancer cells remained unclear. Therefore, the aim of this study is to shed light on the interaction of BCZs with the ER and AhR signaling pathways in breast cancer cells in order to provide a new perspective for clarifying the breast cancer-related adverse outcome pathways that BCZs may trigger. In this study, we selected 5 BCZs to explore the activation effects of BCZs on ER and AhR pathways in ER-positive human breast cancer cells MCF-7. Interactions between the AhR and ER signaling pathways were also studied for BCZs, which has the strongest receptor activation capabilities. The results showed that 1,3,6,8-tetrabromo-9H-carbazole (1368-BCZ) activated both ER and AhR pathways, and upregulated the expression of ER pathway target gene trefoil factor 1 (tff1) and AhR pathway target genes cytochrome P450 1A1 (cyp1a1) and cytochrome P450 1B1 (cyp1b1). The activation of the ER pathway induced by 1368-BCZ was partly dependent on the presence of AhR, while the upregulation of the AhR pathway target genes was further enhanced with the addition of ER blocker. Therefore, 1368-BCZ can activate both the ER and AhR pathways and cause interactions between them. This study supplemented the understanding of the action mechanisms of BCZs in ER-positive breast cancer cells.
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Cross-talk of Bromocarbazoles between Estrogen Receptor Pathway and Aryl Hydrocarbon Receptor Pathway in Human Breast Cancer Cells (MCF-7 Cells)

  • Received Date: 14/03/2022
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Abstract: Polyhalogenated carbazoles are heterocyclic aromatic hydrocarbon compounds with a similar structure to dioxins, which have been detected in environments and organisms. Among them, bromocarbazoles (BCZs) present strong persistence and bioaccumulation potential, and have shown dioxin-like toxicity and endocrine disrupting effects in different organisms, posing potential risks to human health. Studies have shown that BCZs can activate aryl hydrocarbon receptor (AhR) and estrogen receptor (ER) in different types of cells. The ER and AhR pathway are closely related to the occurrence and development of breast cancer. However, the interactions between the ER and AhR pathways induced by BCZs in human breast cancer cells remained unclear. Therefore, the aim of this study is to shed light on the interaction of BCZs with the ER and AhR signaling pathways in breast cancer cells in order to provide a new perspective for clarifying the breast cancer-related adverse outcome pathways that BCZs may trigger. In this study, we selected 5 BCZs to explore the activation effects of BCZs on ER and AhR pathways in ER-positive human breast cancer cells MCF-7. Interactions between the AhR and ER signaling pathways were also studied for BCZs, which has the strongest receptor activation capabilities. The results showed that 1,3,6,8-tetrabromo-9H-carbazole (1368-BCZ) activated both ER and AhR pathways, and upregulated the expression of ER pathway target gene trefoil factor 1 (tff1) and AhR pathway target genes cytochrome P450 1A1 (cyp1a1) and cytochrome P450 1B1 (cyp1b1). The activation of the ER pathway induced by 1368-BCZ was partly dependent on the presence of AhR, while the upregulation of the AhR pathway target genes was further enhanced with the addition of ER blocker. Therefore, 1368-BCZ can activate both the ER and AhR pathways and cause interactions between them. This study supplemented the understanding of the action mechanisms of BCZs in ER-positive breast cancer cells.

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