Experimental study on the inhibitory effect of Halofuginone on NSCLC.

In recent decades, significant advancements have been achieved in non-small cell lung cancer (NSCLC) treatment. However, drug resistance, postoperative recurrence, distant metastasis, and other critical issues arise during NSCLC treatment. Natural products play a crucial role in the development of anti-tumor drugs. Halofuginone (HF) is a derivative of Febrifugine, an extract of Dichroa febrifuga Lour, a traditional Chinese medicine. Recent studies on HF have demonstrated its antitumor activity and great potential for clinical applications. However, its antitumor effects and mechanisms in NSCLC remain unknown. This study aimed to elucidate the antitumor effect of HF on NSCLC and preliminarily explore its mechanism of action. The proliferation-related assay revealed that HF could inhibit the proliferation of lung adenocarcinoma cells HCC827 and H1975. Network pharmacology of HF and NSCLC indicated that HF could induce cellular oxidative stress, and the antitumor effect was related to autophagy, apoptosis, and cell cycle arrest. Experimental analysis using flow cytometry and western blotting confirmed that HF indeed induced autophagy, enhanced apoptosis, and caused cell cycle arrest. The addition of N-acetyl-cysteamine acid inhibits the HF-induced increase in reactive oxygen species levels, inhibits autophagy and apoptosis, and alters cell cycle distribution. The HCC827 transplantation tumor animal model established that HF substantially inhibited the growth of transplanted tumors. These findings suggest that HF exerts a significant inhibitory effect on NSCLC in vivo and in vitro. The inhibitory effect of HF on NSCLC was associated with the increase of ROS in tumor cells, induction of autophagy and apoptosis, and cell cycle arrest.