Transcription factor Nrf2 regulating the interaction of p16 facilitates hydroquinone-induced malignant transformation of TK6 cells by accelerating cell proliferation

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. • Nrf2-Keap1 signaling pathway is continuously activated under long-term HQ treatment. • Nrf2 inhibits cell proliferation and prevented cells from entering S phase from G1 phase. • Nrf2 activates the p16/Rb signaling pathway by binding to p16.