Dihydroartemisinin induces ferroptosis in pancreatic cancer cells by the regulation of survival prediction-related genes

Abstract

Background: Ferroptosis is a new therapeutic modality that holds promise for pancreatic cancer treatment. Dihydroartemisinin is the first generation of artemisinin derivatives with antimalarial activity, and it exerts anticancer activity through iron-dependent reactive oxygen species generation. This study assessed the potential value of dihydroartemisinin to induce ferroptosis in pancreatic cancer. Methods: The mRNA expression profiles, along with the corresponding clinical information of individuals diagnosed with pancreatic cancer, were acquired from publicly accessible repositories. We analyzed the association of ferroptosis-related gene expression with pancreatic cancer overall survival via The Cancer Genome Atlas. Utilizing molecular docking techniques, we evaluated the potential binding configurations of dihydroartemisinin with genes associated with ferroptosis. Moreover, in-vitro experiments were performed to verify these predicted outcomes. Results: In the The Cancer Genome Atlas cohort, there were significant differences in the expression levels of ten genes associated with ferroptosis when comparing pancreatic cancer tissues with normal tissues. Among them, a strong association between NQO1 expression and unfavorable prognosis was observed. Dihydroartemisinin can regulate target gene expression by interacting with the corresponding binding site, and a ferroptosis inhibitor could reverse the above events. Conclusion: The NQO1 gene, which is associated with ferroptosis, emerges as a robust and autonomous prognostic indicator for individuals with pancreatic cancer. Dihydroartemisinin may contribute to pancreatic cancer progression via the regulation of ferroptosis.