title: Piceatannol suppresses breast cancer cell invasion through the inhibition of MMP-9: involvement of PI3K/AKT and NF-κB pathways.
abstract: Cancer invasion and metastasis are the main causes of treatment failure and death in cancer patients. Piceatannol (3,3',4,5'-tetrahydroxy-trans-stilbene) is a natural analogue of resveratrol. This study investigated the anti-invasive mechanisms of piceatannol in MDA-MB-231 cells. Piceatannol significantly reduced serum-induced cell invasion and migration as well as adhesion without affecting the viability of cells. Furthermore, piceatannol markedly inhibited matrix metalloproteinase-9 (MMP-9) activity and expression at both protein and mRNA levels. Piceatannol attenuated phosphoinisitide-3-kinase (PI3K) and phosphorylation of AKT and mammalian target of rapamycin (mTOR), whereas phosphatase and tensin homologue (PTEN) was increased. Moreover, piceatannol inhibited nuclear factor kappa B (NF-κB) transcriptional activity and DNA binding of NF-κB on MMP-9 promoter. In addition, piceatannol diminished NF-κB nuclear translocation through blocking the inhibitor of NF-κB alpha (IκBα) phosphorylation in the cytoplasm. These results proposed piceatannol as a potential anti-invasive agent by inhibiting MMP-9 involved in PI3K/AKT and NF-κB pathways.
authors.affiliation: Cancer Preventive Material Development Research Center, College of Oriental Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Hyun Suk
authors.initials: HS
authors.lastname: Ko
authors.forename: Hyo-Jeong
authors.initials: HJ
authors.lastname: Lee
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Eun-Ok
authors.initials: EO
authors.lastname: Lee
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D013267:Stilbenes; C041525:3,3',4,5'-tetrahydroxystilbene; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020780:Matrix Metalloproteinase 9