Abstract
Nitidine chloride (NC) possesses anticancer properties in various types of human malignancies. However, the effects of NC on lung cancer cells have not been elucidated. Moreover, the molecular mechanism of NC-involved antitumor activity is unclear. Therefore, we aimed to determine the biological effect of NC and the underlying molecular insights in lung cancer cells. The antineoplastic function of NC was assessed by MTT assays, Annexin V-FITC/PI apoptosis assay, wound healing analysis, and Transwell chamber migration and invasion assay in lung cancer cells. NEDD4 modulation was evaluated by western blotting assays of lung cancer cells after NC treatments. NEDD4 overexpression and downregulation were employed to validate the critical role of NEDD4 in the NC-mediated tumor suppressive effects. We found that NC suppressed cell viability, migration and invasion, but induced apoptosis in lung cancer cells. Mechanistic exploration revealed that NC exhibited its antitumor effects by reducing NEDD4 expression. Furthermore, our rescue experiments dissected that overexpression of NEDD4 abrogated the NC-mediated antineoplastic effects in lung cancer cells. Consistently, downregulation of NEDD4 enhanced the NC-induced anticancer effects. Thus, NC is a promising antitumor agent in lung cancer, indicating that NC might have potential therapeutic applications in the treatment of lung cancer.
Highlights
Lung cancer is one of the most common malignancies worldwide
We found that Nitidine chloride (NC) reduced cell viability in a concentration-dependent manner in lung cancer cells (Figure 1A)
6 μM NC resulted in a 50% reduction in cell viability in H1299 cells but an approximately 70% decrease in cell viability in H460 cells, indicating that H460 cells are more sensitive to NC treatment than H1299 cells (Figure 1A)
Summary
Lung cancer is one of the most common malignancies worldwide. It is expected that 228,820 new cases of lung cancer will be diagnosed and 112,520 patients will die due to lung cancer in the United States of America in 2020 [1]. Deaths due to lung cancer contribute to almost 25% of all cancer deaths in the USA [1]. Treatments for this disease, including surgery, chemotherapy, and immunotherapy, have been improved. The 5-year survival rate in lung cancer patients is approximately 19%. Identification of new drugs with fewer side-effects for lung cancer treatments is urgently needed
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