Guangyi Chen

Background: Non-small cell lung carcinoma (NSCLC) is the most prevalent form of lung cancer, and its progression is closely associated with 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 STAT3-targeting compounds from the traditional Chinese medicine Psoralea corylifolia and to evaluate their anti-NSCLC activities, with particular attention to reactive oxygen species (ROS) regulation. Methods: The SPR biosensor immobilized with STAT3 was used to screen and enrich STAT3-binding constituents of Psoralea corylifolia, and to determine ligand-STAT3 affinities. Molecular docking was performed to characterize interactions within the STAT3 SH2 domain. Functional effects were assessed in A549 cells using proliferation and scratch migration assays. Antioxidant capacity was evaluated via hydroxyl radical and superoxide anion scavenging assays, and intracellular ROS levels were measured in hydrogen peroxide (H₂O₂)-induced oxidative stress models in human umbilical vein endothelial cells (HUVECs) and A549 cells. Results: SPR analysis showed that psoralen and isopsoralen bind 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. Both compounds inhibited A549 proliferation and reduced migration. Beyond direct STAT3 inhibition, both compounds demonstrated notable free radical scavenging activity. In a H₂O₂-induced oxidative stress model, pretreatment with psoralen or isopsoralen significantly reduced ROS levels in HUVECs, while increasing ROS accumulation in A549 lung cancer cells. Conclusions: This work identifies psoralen and isopsoralen as novel dual-function STAT3 inhibitors that exert anti-NSCLC effects through combined STAT3 suppression and context-dependent ROS modulation, and demonstrates the utility of SPR for screening bioactive natural products.

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.