title: Anti-metastatic effect of rhodomyrtone from Rhodomyrtus tomentosa on human skin cancer cells.
abstract: This study focused on the inhibitory effect of rhodomyrtone, a bioactive compound isolated from the leaves of Rhodomyrtus tomentosa (Aiton) Hassk., on cancer metastasis in epidermoid carcinoma A431 cells and on the verification of the underlying related molecular mechanisms of this event. We demonstrated that rhodomyrtone at the subcytotoxic concentration (0.5 and 1.5 µg/ml) exhibited pronounced inhibition of cancer metastasis by reducing cell migration, cell adhesive ability and cell invasion of A431 cells in a dose-dependent manner. Data demonstrated that rhodomyrtone could inhibit the focal adhesion kinase (FAK) and phosphorylation of protein kinase B (AKT), c-Raf, extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 MAPK involved in the downregulation the enzyme activities and protein expression of matrix metalloproteinase-2 (MMP-2) and MMP-9. Moreover, we found that rhodomyrtone increased the expression of TIMP-1 and TIMP-2, which are inhibitors of MMP-9 and MMP-2, respectively. Rhodomyrtone also inhibited the expression of NF-κB and phosphorylation of NF-κB in a dose-dependent manner. These results suggested that rhodomyrtone inhibited A431 cell metastasis by reducing MMP-2/9 activities and expression through inhibiting ERK1/2, p38 and FAK/Akt signaling pathways via NF-κB activities. This finding suggested that rhodomyrtone may be a novel antimetastasis agent for treatment of skin cancer cells.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Srinakharinwirot University, Bangkok 10110, Thailand.
authors.forename: Malatee
authors.initials: M
authors.lastname: Tayeh
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Srinakharinwirot University, Bangkok 10110, Thailand.
authors.forename: Sirinun
authors.initials: S
authors.lastname: Nilwarangoon
authors.affiliation: Department of Chemistry, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand.
authors.forename: Wilawan
authors.initials: W
authors.lastname: Mahabusarakum
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Srinakharinwirot University, Bangkok 10110, Thailand.
authors.forename: Ramida
authors.initials: R
authors.lastname: Watanapokasin
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D027822:Myrtaceae / Q000737:chemistry; D016328:NF-kappa B / Q000096:biosynthesis / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis / Q000188:drug therapy* / Q000517:prevention & control*; D010766:Phosphorylation / Q000187:drug effects; D028321:Plant Preparations / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis; D044004:Xanthones / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D028321:Plant Preparations; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D044004:Xanthones; C541823:rhodomyrtone; D019716:Tissue Inhibitor of Metalloproteinase-2; D051416:Focal Adhesion Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt; D019908:Proto-Oncogene Proteins c-raf; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9