Andrographolide promoted ferroptosis to repress the development of non-small cell lung cancer through activation of the mitochondrial dysfunction

Ferroptosis, a form of regulated cell death by lipid peroxidation, was currently considered as a key factor affecting the occurrence and progression in various cancers. Andrographolide (ADE), a major effective ingredient of Andrographis paniculate, has proven to have a substantial anti-tumor effect on multiple cancer types. However, the function and underlying mechanism of ADE in Non-Small Cell Lung Cancer remain unclear. CCK8 assay, colony-formation assay, flow cytometry, scratch test, transwell assay, western blotting, ferroptosis analysis and mitochondria analysis were performed to reveal the role and underlying mechanisms of ADE in NSCLC cell lines (H460 and H1650). In vivo, xenograft model and lung metastatic model were performed to verify the effect of ADE on the growth and metastasis of NSCLC. In this present study, we demonstrated that treatment with ADE could inhibit cell growth and metastases through eliciting ferroptosis in vitro an in vivo. The IC50 of ADE in H460 and H1650 cells were 33.16 μM and 32.45 μM respectively. In Lewis xenografted animals, i.p. ADE repressed relative tumor growth (p