title: Inhibition of invasion and experimental metastasis of murine melanoma cells by Ipomoea obscura (L.) is mediated through the down-regulation of inflammatory mediators and matrix-metalloproteinases.
abstract: In this study, we tested the anti-metastatic activity of Ipomoea obscura extract and elucidated its underlying mechanisms by in vitro system using B16F-10 melanoma cells and in vivo experimental lung metastasis model. I. obscura suppressed proliferation, invasion and migration of highly metastatic B16F-10 melanoma cells in vitro. I. obscura could also decrease transcription factors such as nuclear factor kappaB (NF-kappaB) and activator protein (AP-1) in B16F-10 melanoma cells. Administration of I. obscura resulted significant suppression of B16F-10 melanoma induced tumor nodule formation and enhanced the survival of tumor-bearing mice. The level of various biochemical parameters associated with lung metastasis were also found to be decreased by the I. obscura treatment. A significant down regulation in the expression of inflammatory mediators such inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), pro-inflammatory cytokines related to tumor metastasis was observed by the treatment with I. obscura. Higher expression levels of pro-metastatic genes such as matrix metalloproteinase (MMP-2 and 9), was observed in the metastatic group, but these were down-regulated by the treatment with I. obscura. The endogenous MMP inhibitor tissue inhibitor of metalloproteinases (TIMP) was found to be up-regulated by I. obscura treatment. Our results indicate that the anti- invasive and antimetastatic effect of I. obscura is mediated at least in part by reduced expression of inflammatory mediators by inhibiting NF-kappaB signaling with their downstream targets iNOS, COX-2 and pro-inflammatory cytokine and also by inhibiting MMP-9 and MMP-2.
authors.affiliation: Amala Cancer Research Centre, Amala Nagar, Thrissur, Kerala, India.
authors.forename: Thayele Purayil
authors.initials: TP
authors.lastname: Hamsa
authors.forename: Girija
authors.initials: G
authors.lastname: Kuttan
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D027741:Ipomoea / Q000737:chemistry*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009362:Neoplasm Metastasis / Q000517:prevention & control; D010936:Plant Extracts / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018836:Inflammation Mediators; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D010936:Plant Extracts; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9