Pomolic Acid Induces Ferroptosis-Mediated Cell Death in Non-small Cell Lung Cancer

Wenbin Ji¹Yanbin Zhang¹Wenhao Ji²Hui Zhang³Biao Qin¹Xiao-Liang Xing^3*Zaiqi Zhang^3*

• ¹Ningxia Medical University, Yinchuan, China
• ²Gannan Medical University, Ganzhou, Jiangxi Province, China
• ³Hunan University of Medicine, Huaihua, Hunan Province, China

Pomolic Acid (PA), a bioactive compound derived from Potentilla freyniana Bornm., is used palliatively for non-small cell lung cancer (NSCLC) in China's Dongzu region, with some reports of clinical efficacy. However, the specific underlying molecular mechanism remains unclear. In this study, we utilize network pharmacological analysis to identify the core targets of PA., and in vitro functional studies are employed to explore its function and potential mechanisms.The results indicate that PA effectively induces cell death and inhibits proliferation in NSCLC cells. Characteristic hallmarks of ferroptosis, including depletion of the endogenous antioxidant glutathione (GSH), iron (Fe2+)-dependent lipid peroxidation, and upregulation of reactive oxygen species (ROS), are observed. We find that the protein expression levels of key anti-ferroptosis factors (SLC40A1, SLC7A11, and GPX4) are significantly downregulated, while the levels of proferroptosis proteins (ACSL4 and HO-1) are markedly upregulated. Additionally, significantly reduced mRNA expression levels of genes negatively regulating ferroptosis, such as GPX4, SLC7A11, and NRF2, are revealed by quantitative PCR (qPCR) analysis. Overall, these findings suggest that PA exerts its anti-cancer effects primarily through the induction of ferroptosis, positioning PA as a potential therapeutic agent for NSCLC treatment.