Urokinase-type plasminogen activator expression and Rac1/WAVE-2/Arp2/3 pathway are blocked by pterostilbene to suppress cell migration and invasion in MDA-MB-231 cells

• Published in: Bioorganic & medicinal chemistry letters 2014-02, Vol.24 (4), p.1176-1179
• Main Authors: Ko, Hyun Suk, Kim, Ji Sung, Cho, Sun Mi, Lee, Hyo-Jeong, Ahn, Kwang Seok, Kim, Sung-Hoon, Lee, Eun-Ok
• Format: Article
• Language: English
• Subjects: Actin-Related Protein 2-3 Complex - antagonists & inhibitors; Actin-Related Protein 2-3 Complex - metabolism; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Cell Movement - drug effects; Cell Proliferation - drug effects; Cell Survival - drug effects; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; Molecular Conformation; Neoplasm Invasiveness - pathology; Neoplasm Invasiveness - prevention & control; rac1 GTP-Binding Protein - antagonists & inhibitors; rac1 GTP-Binding Protein - metabolism; Stilbenes - chemical synthesis; Stilbenes - chemistry; Stilbenes - pharmacology; Structure-Activity Relationship; Urokinase-Type Plasminogen Activator - antagonists & inhibitors; Urokinase-Type Plasminogen Activator - biosynthesis; Urokinase-Type Plasminogen Activator - metabolism; Wiskott-Aldrich Syndrome Protein Family - antagonists & inhibitors; Wiskott-Aldrich Syndrome Protein Family - metabolism
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2013.12.115

Breast cancer is the most common malignancy among females, and cancer invasion and metastasis are the leading causes of cancer death in breast cancer patients. Pterostilbene, a naturally occurring dimethylether analogue of resveratrol, has been demonstrated to possess anti-cancer effects. However, inhibitory effects of pterostilbene on cell migration and invasion and its underlying mechanisms are not fully understood. In this study, we investigated the anti-invasive mechanisms of pterostilbene in human breast cancer cell line MDA-MB-231 cells. Pterostilbene effectively inhibited serum-induced migration and invasion without affecting the viability of breast cancer cells. The mRNA expression and activity of urokinase-type plasminogen activator (uPA) were markedly reduced by pterostilbene treatment. Moreover, pterostilbene attenuated nuclear factor κB (NF-κB) transcriptional activity and DNA binding of NF-κB on uPA promoter. In addition, pterostilbene significantly impaired the activity of Rac1 and the expression of WASP-family verprolin-homologous protein-2 (WAVE-2) and actin-related protein 2/3 (Arp2/3). Overall, these results suggest that pterostilbene caused considerable suppression of cell migration and invasion through blocking NF-κB-mediated uPA expression and Rac1/WAVE/Arp2/3 pathway.