Vernonia cinerea Less. inhibits tumor cell invasion and pulmonary metastasis in C57BL/6 mice.
The effect of Vernonia cinerea Less. extract on the inhibition of lung metastasis induced by B16F-10 melanoma cells was studied in C57BL/6 mice. V cinerea extract significantly (P < .001) inhibited lung tumor formation (78.8%) and significantly increased the life span (72.5%). Moreover, lung collagen hydroxyproline, uronic acid, and hexosamine and also serum sialic acid, γ-glutamyltransferase (GGT), and vascular endothelial growth factor (VEGF) levels were found to be significantly (P < .001) lower in treated animals compared with untreated controls. Histopathological analysis of the lung tissues also correlated with these findings. V cinerea treatment significantly inhibited the invasion of B16F-10 melanoma cells across the collagen matrix of the Boyden chamber. V cinerea also inhibited the migration of B16F-10 melanoma cells across a polycarbonate filter in vitro. It downregulated the production and expression of proinflammatory cytokines such as TNF (tumor necrosis factor)-α, IL (interleukin)-1β, IL-6, and GM-CSF (granulocyte monocyte colony-stimulating factor). V cinerea extract administration could suppress or downregulate the expression of matrix metalloproteinase (MMP)-2, MMP-9, lysyl oxidase, prolyl hydroxylase, K-ras, extracellular signal-regulated kinase (ERK)-1, ERK-2, and VEGF and also upregulate the expression of nm-23, tissue inhibitor of metalloproteinase (TIMP-1), and TIMP-2 in the lung tissue of metastasis-induced animals. It also inhibited the protein expression of MMP-2 and MMP-9 in gelatin zymographic analysis of B16F-10 cells. These results indicate that V cinerea could inhibit the metastatic progression of B16F-10 melanoma cells in C57BL/6 mice by regulating MMPs, VEGF, prolyl hydroxylase, lysyl oxidase, ERK-1, ERK-2, TIMPs, nm23, and proinflammatory cytokine gene expression in metastatic lung tissue.
Amala Cancer Research Centre, Thrissur, Kerala, India.
Poyil
P
Pratheeshkumar
Girija
G
Kuttan
D000818:Animals; D019659:Asteraceae / Q000737:chemistry*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000378:metabolism; D016207:Cytokines / Q000097:blood / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics; D005780:Gelatin / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D006595:Hexosamines / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control* / Q000556:secondary*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D008546:Melanoma, Experimental / Q000097:blood / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D054778:NM23 Nucleoside Diphosphate Kinases / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009929:Organ Size / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase / Q000235:genetics; D011393:Procollagen-Proline Dioxygenase / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D012794:Sialic Acids / Q000097:blood; D016019:Survival Analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics; D014407:Tumor Cells, Cultured; D014574:Uronic Acids / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000235:genetics; D005723:gamma-Glutamyltransferase / Q000097:blood
D017077:Culture Media, Conditioned; D016207:Cytokines; D006595:Hexosamines; D054778:NM23 Nucleoside Diphosphate Kinases; D010936:Plant Extracts; D012794:Sialic Acids; C560825:Timp1 protein, mouse; D019715:Tissue Inhibitor of Metalloproteinase-1; D014574:Uronic Acids; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D019716:Tissue Inhibitor of Metalloproteinase-2; D005780:Gelatin; D003094:Collagen; D011393:Procollagen-Proline Dioxygenase; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase; D005723:gamma-Glutamyltransferase; D048049:Extracellular Signal-Regulated MAP Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; D016283:Proto-Oncogene Proteins p21(ras); D006909:Hydroxyproline