Allicin: A natural weapon against Taxol resistance in non-small cell lung cancer through Cathepsin B inhibition and lysosomal-autophagy disruption

Abstract

Drug resistance in non-small cell lung cancer (NSCLC) limits its therapeutic efficacy. Allicin may help to solve the problem of Taxol resistance in NSCLC. This study aimed to explore the potential mechanism by which allicin reverses Taxol resistance in NSCLC. The potential mechanism of allicin reversing Taxol resistance in vitro was evaluated using cytotoxicity assays, evaluation of cell autophagy and lysosomal function. In addition, the in vivo model was established to evaluate the effectiveness of allicin in reversing Taxol resistance. The results showed that allicin effectively inhibited cell proliferation, induced apoptosis, and reversed Taxol resistance. It inhibits P-gp expression, reduces drug efflux, and disrupts cell autophagy. In particular, allicin inhibited Cathepsin B (CTSB), disrupted lysosomal function, blocked autophagy flux, reduced mitochondrial membrane potential, and enhanced the sensitivity to Taxol. Allicin combined with Taxol significantly inhibited the growth of tumor nodules and reduced their number, demonstrating its potential to reverse Taxol resistance in vivo. In summary, allicin reversed Taxol resistance by inhibiting P-gp and CTSB activity and disrupting the lysosomal-autophagy pathway. These findings highlight the potential of allicin for cancer treatment and drug development.