Abstract
BackgroundNorcantharidin (NCTD) is known to impact on cell progression in many cancers; however, its activity in non-small cell lung cancer (NSCLC) has not yet been characterized. In the present study, we set out to determine the cytotoxic effects of NCTD on the proliferation and apoptosis on A549 cells and their underlying mechanisms.MethodsNSCLC cell line A549 cells were cultured. A549 cells were treated with different concentrations of NCTD. Cell proliferation was detected by MTT and cell clone formation assay. Cell cycle and apoptosis were detected by flow cytometry. After A549 cells were treated with NCTD for 24 hours, the mitochondrial membrane potential was measured. The protein expression of Bcl-2, Bax, light chain 3 (LC3), et al. was tested by western blot. The expression of LC3 and Tom20 protein was detected by immunofluorescence.ResultsNCTD suppressed the proliferation of NSCLC cells while decreasing mitochondrial membrane potential and inducing G2/M phase arrest. NCTD induced apoptosis, as demonstrated by increased B-cell lymphoma 2/Bcl-2-associated X protein and Bcl-2-associated X protein/myeloid cell leukemia 1 ratios. Aside from autophagy, NCTD induced mitophagy, with an increase in LC3 expression and a decrease in sequestosome 1 (p62) expression in the cytoplasm, accompanied by increased levels of Phospho-adenosine 5’-monophosphate -activated protein kinase (p-AMPK), Phospho-c-Jun NH2-Terminal Kinase (p-JNK), and Phospho-c-jun (p-c-jun) and a decreased level of Phospho-protein kinase B (p-AKT).ConclusionsThis study has elucidated that NCTD restrains NSCLC cell progression via regulation of AMPK/mammalian target of rapamycin (mTOR)/uncoordinated 51-like kinase 1 (ULK1)/JNK pathways. This evidence provides insight into a novel treatment for NSCLC.
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