Antiproliferative and Antimetastatic Effects of Praeruptorin C on Human Non-Small Cell Lung Cancer Through Inactivating ERK/CTSD Signalling Pathways.

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.

• Authors: Chien-Ming Liu, Huan-Ting Shen, Yi-An Lin, Yung-Luen Yu, Yong-Syuan Chen, Chung-Jung Liu, Yi-Hsien Hsieh
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 25 Issue 7 (Apr 01 2020) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 32244796 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents, Phytogenic
• Coumarins
• Drugs, Chinese Herbal
• praeruptorin C
• Extracellular Signal-Regulated MAP Kinases
• CTSD protein, human
• Cathepsin D

Topics

• Antineoplastic Agents, Phytogenic (pharmacology)
• Carcinoma, Non-Small-Cell Lung (drug therapy, metabolism, pathology)
• Cathepsin D (genetics, metabolism)
• Cell Cycle Checkpoints (drug effects)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cell Survival
• Coumarins (pharmacology)
• Drugs, Chinese Herbal
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Gene Expression Regulation
• Humans
• Lung Neoplasms (drug therapy, metabolism, pathology)
• Neoplasm Metastasis
• Signal Transduction (drug effects)