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.
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.
Cancer Preventive Material Development Research Center, College of Korean Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
Hyun Suk
HS
Ko
Cancer Preventive Material Development Research Center, College of Korean Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
Ji Sung
JS
Kim
Cancer Preventive Material Development Research Center, College of Korean Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
Sun Mi
SM
Cho
Cancer Preventive Material Development Research Center, College of Korean Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
Hyo-Jeong
HJ
Lee
Cancer Preventive Material Development Research Center, College of Korean Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
Kwang Seok
KS
Ahn
Cancer Preventive Material Development Research Center, College of Korean Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
Sung-Hoon
SH
Kim
Cancer Preventive Material Development Research Center, College of Korean Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea. Electronic address: leook@khu.ac.kr.
Eun-Ok
EO
Lee
D051376:Actin-Related Protein 2-3 Complex / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008968:Molecular Conformation; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000517:prevention & control*; D013267:Stilbenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism
D051376:Actin-Related Protein 2-3 Complex; D000970:Antineoplastic Agents; C107953:RAC1 protein, human; D013267:Stilbenes; C120152:WASF2 protein, human; D051300:Wiskott-Aldrich Syndrome Protein Family; C107773:pterostilbene; D014568:Urokinase-Type Plasminogen Activator; D020830:rac1 GTP-Binding Protein
Arp2/3; Invasion; MDA-MB-231 cells; Migration; NF-κB; Pterostilbene; Rac1; WAVE; uPA