Dongguan Key Laboratory of Environmental Medicine, The First Dongguan Affiliated Hospital, School of Public Health, Guangdong Medical University, Dongguan 523808, China.
Ecotoxicol Environ Saf. 2024 Oct 15;285:117142. doi: 10.1016/j.ecoenv.2024.117142. Epub 2024 Oct 2.
The nuclear factor erythroid 2-related factor 2 (Nrf2) is overexpressed in multiple tumor cells. Nevertheless, the role of Nrf2 in malignant transformation induced by hydroquinone (HQ) is unknown. Here, we hypothesized that Nrf2 might participate in HQ-induced malignant transformation of TK6 cells, a line of normal human lymphoblastoid cells, by accelerating cell proliferation and regulating cell cycle progression. The data indicated that TK6 cells chronically exposed to HQ continuously activated Nrf2-Keap1 signaling pathway. Furthermore, we found that defects in Nrf2 inhibited cell proliferation and prevented cells from entering S phase from G1 phase. Mechanistically, Nrf2 is involved in cell cycle abnormalities induced by prolonged exposure to HQ by binding to p16, thereby activating the p16/Rb signaling pathway. Taken together, Nrf2 might be a potential driver of carcinogenesis that promotes malignant cell proliferation and affects cell cycle distribution.
核因子红细胞 2 相关因子 2（Nrf2）在多种肿瘤细胞中过度表达。然而，Nrf2 在对苯二酚（HQ）诱导的恶性转化中的作用尚不清楚。在这里，我们假设 Nrf2 可能通过加速细胞增殖和调节细胞周期进程参与 HQ 诱导的正常人类淋巴母细胞系 TK6 细胞的恶性转化。数据表明，长期暴露于 HQ 的 TK6 细胞持续激活 Nrf2-Keap1 信号通路。此外，我们发现 Nrf2 的缺陷抑制细胞增殖并阻止细胞从 G1 期进入 S 期。从机制上讲，Nrf2 通过与 p16 结合参与 HQ 长期暴露引起的细胞周期异常，从而激活 p16/Rb 信号通路。总之，Nrf2 可能是促进恶性细胞增殖和影响细胞周期分布的致癌驱动因素。
