Puerarin Inhibits Nasopharyngeal Carcinoma Cell Growth by Inducing Ferroptosis with Involvement of the SLC7A11/GSH/GPX4 Axis

Abstract

Nasopharyngeal carcinoma (NPC) is a malignant tumour with a high incidence in Southeast Asia and southern China. Currently, there is a lack of effective targeted therapy strategies for NPC in clinical practice, thus urgently necessitating the development of new treatment methods. Puerarin, the primary active isoflavonoid derived from the traditional Chinese medicine Pueraria lobata, exhibits anti-tumour efficacy in multiple cancer types. However, its function and underlying mechanism in NPC remain unclear. In this study, the human NPC cell lines C666-1 and HK-1 were treated with different concentrations of puerarin either alone or in combination with the ferroptosis inhibitor Fer-1. We employed a series of techniques to investigate the anti-tumour effects, including assessing cell viability, IC50, and apoptosis via CCK-8 and flow cytometry, measuring the levels of glutathione (GSH), malondialdehyde (MDA), and intracellular iron with biochemical detection; detecting reactive oxygen species (ROS) using immunofluorescence, and analyzing the expression of ferroptosis-related proteins GPX4 and SLC7A11 through Western blotting. The findings indicated that puerarin suppressed the viability of C666-1 and HK-1 cells in a dose-dependent manner, with IC50 values of 117.9 µM (24 h) and 85.14 µM (48 h) for C666‑1, and 89.39 µM (24 h) and 50.58 µM (48 h) for HK‑1. Puerarin induced apoptotic cell death, lowered GSH concentrations, and elevated levels of MDA, intracellular iron, and ROS. Meanwhile, puerarin reduced the protein expression of GPX4 and SLC7A11. The Fer-1 reversed all the aforementioned effects of puerarin. This in vitro study suggests that puerarin inhibits NPC cell growth by inducing ferroptosis, providing preliminary phenotypic evidence for further in vivo and mechanistic studies.