Psoralen and Isopsoralen from Psoralea corylifolia Suppress NSCLC by Dual Mechanisms: STAT3 Inhibition and ROS Modulation

Non-small cell lung carcinoma (NSCLC) is the most prevalent form of lung cancer, and its progression is strongly driven by the constitutive activation of signal transducer and activator of transcription 3 (STAT3). This study used surface plasmon resonance (SPR) technology to develop a STAT3-targeting recognition system and identify natural inhibitors from the traditional Chinese medicine Psoralea corylifolia. SPR analysis showed that psoralen and isopsoralen bind effectively to STAT3, with equilibrium dissociation constants (KD) of 80.92 µM and 28.11 µM, respectively. Molecular docking further confirmed their interaction with the STAT3 SH2 domain. Beyond direct STAT3 inhibition, both compounds demonstrated notable free radical scavenging activity. In a hydrogen peroxide (H₂O₂)-induced oxidative stress model, pretreatment with psoralen or isopsoralen significantly reduced reactive oxygen species (ROS) levels in human umbilical vein endothelial cells (HUVECs), while increasing ROS accumulation in A549 lung cancer cells. This combined ability to inhibit STAT3 and regulate redox homeostasis underlies their anti-NSCLC effects, including strong suppression of cancer cell proliferation and migration. Importantly, neither compound exhibited significant cytotoxicity in normal cells, indicating favorable selectivity. This work identifies psoralen and isopsoralen as novel dual-function STAT3 inhibitors and demonstrates the utility of SPR for screening bioactive natural products for targeted NSCLC therapy.