College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi 030006, PR China.
College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi 030006, PR China.
Sci Total Environ. 2024 Nov 20;952:175878. doi: 10.1016/j.scitotenv.2024.175878. Epub 2024 Sep 1.
Hydroxy-polycyclic aromatic hydrocarbons (OH-PAHs) are a growing worldwide concern because of their persistence, ubiquity, and toxicity. Nonetheless, research on the toxicological mechanisms of OH-PAHs remains sparse, particularly concerning the risk of liver cancer. This study evaluated the effects of OH-PAHs on disrupting estrogen receptor α (ERα) and subsequently facilitating hepatocellular invasion and metastasis. Results revealed that all six OH-PAHs exhibited ERα agonistic activities at noncytotoxic levels, which were partially validated using molecular docking (MD) and molecular dynamics simulations (MDS). Furthermore, OH-PAHs with ERα agonistic properties stimulated a concentration-dependent increase in the migration and invasion of HepG2 cells. In addition, they disturbed the expression of target genes associated with epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM), and the invasion effects were significantly reversed by adding an ERα antagonist. Our results suggest an essential role of ERα in the metastasis of liver cancer cells induced by OH-PAHs and emphasize their potential ecological and health hazards.
羟基多环芳烃（OH-PAHs）因其持久性、普遍性和毒性而引起了全球范围内的关注。然而，OH-PAHs 的毒理学机制研究仍然很少，特别是关于肝癌风险的研究。本研究评估了 OH-PAHs 对破坏雌激素受体 α（ERα）并随后促进肝细胞侵袭和转移的影响。结果表明，所有六种 OH-PAHs 在非细胞毒性水平下均表现出 ERα 激动活性，这部分通过分子对接（MD）和分子动力学模拟（MDS）得到了验证。此外，具有 ERα 激动特性的 OH-PAHs 刺激 HepG2 细胞的迁移和侵袭呈浓度依赖性增加。此外，它们还扰乱了与上皮-间充质转化（EMT）和细胞外基质（ECM）相关的靶基因的表达，并且通过添加 ERα 拮抗剂可以显著逆转侵袭作用。我们的研究结果表明，ERα 在 OH-PAHs 诱导的肝癌细胞转移中起着重要作用，并强调了它们的潜在生态和健康危害。
