Abstract
Praeruptorin C (PC) reportedly has beneficial effects in terms of antiinflammation, antihypertension, and antiplatelet aggregation, and it potentially has anticancer activity. However, the effect of PC on human non–small cell lung cancer (NSCLC) is largely unknown. Compared with the effects of praeruptorin A and praeruptorin B, we observed that PC significantly suppressed cell proliferation, colony formation, wound closure, and migration and invasion of NSCLC cells. It induced cell cycle arrest in the G0/G1 phase, downregulated cyclin D1 protein, and upregulated p21 protein. PC also significantly reduced the expression of cathepsin D (CTSD). In addition, the phosphorylation/activation of the ERK1/2 signalling pathway was significantly suppressed in PC-treated NSCLC cells. Cotreatment with PC and U0126 synergistically inhibited CTSD expression, cell migration, and cell invasion, which suggests that the ERK1/2 signalling pathway is involved in the downregulation of CTSD expression and invasion activity of NSCLC cells by PC. These findings are the first to demonstrate the inhibitory effects of PC in NSCLC progression. Therefore, PC may represent a novel strategy for treating NSCLC.
Highlights
Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer-related deaths globally because of its poor prognosis [1]
Our findings demonstrated that Praeruptorin C (PC) treatment inhibits cell proliferation, invasive motility, and Cathepsin D (CTSD) expression by suppressing the ERK1/2 signalling pathway
We compared the effects of praeruptorin A (PA), praeruptorin B (PB), and PC on cell viability and cytotoxicity in two human lung cancer cell lines, A549 and H1299
Summary
Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer-related deaths globally because of its poor prognosis [1]. 2.09 million new cases of lung cancer are reported yearly (11.6% of all cancer cases), resulting in. 1.76 million deaths (18.4% of all cancer-related deaths) worldwide [2]. Non–small cell lung cancer (NSCLC) is the most common type of lung cancer, comprising 85% of all lung cancers. Metastasis and drug resistance are the main causes of death in lung cancer patients [5]. 66% of patients exhibit metastatic lesions when they are first diagnosed with lung cancer [6]. Inhibition of metastasis is a critical topic in cancer research
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