title: Inhibition of metastasis of B16F-10 melanoma cells in C57BL/6 mice by an extract of Calendula officinalis L flowers.
abstract: OBJECTIVE
  To determine the effect of a Calendula officinalis flower extract on lung metastasis by B16F-10 melanoma cells in C57BL/6 mice.
  
  
  METHODS
  Male mice were injected with B16F-10 melanoma cells through the tail vein and simultaneously treated with C.officinalis flower extract. Parameters studied were lung tumor nodule count, life span of animals, gamma glutamyl transpeptidase activity, sialic acid, TNF-α, IL-1β, IL-6, IL-2, GM-CSF, VEGF and TIMP-1 levels in serum, and lung hydroxyproline, uronic acid and hexosamine levels, as well as histopathological features. Effects of C.officinalis on the expression of various genes involved in metastasis like matrix metalloproteases (MMPs), tissue inhibitor of metalloproteases (TIMPs), prolyl hydoxylase, lysyl oxidase, nm23, and proinflammatory cytokines were also investigated.
  
  
  RESULTS
  Simultaneous administration of C. officinalis extract to tumor bearing C57BL/6 mice reduced the lung tumor nodules by 74% with 43.3% increase in life span. Elevated levels of hydroxyproline, uronic acid, hexosamine, serum sialic acid and γ-glutamyl transpeptidase in the metastatic controls were found to be significantly lowered in the C. officinalis treated animals. The extract also inhibited expression of MMP-2, MMP-9, prolyl hydroxylase and lysyl oxidase and activated TIMP-1 and TIMP-2 and downregulated proinflammatory cytokines.
  
  
  CONCLUSIONS
  The present investigation indicated antimetastatic effects of Calendula officinalis flowers through the inhibition of key enzymes involved in processes of metastasis.
authors.affiliation: Department of Biochemistry, Amala Cancer Research Centre, Amala Nagar, Thrissur, Kerala, India. kcpreethi@gmail.com
authors.forename: Korangath C
authors.initials: KC
authors.lastname: Preethi
authors.forename: Kodappully S
authors.initials: KS
authors.lastname: Siveen
authors.forename: Ramadasan
authors.initials: R
authors.lastname: Kuttan
authors.forename: Girija
authors.initials: G
authors.lastname: Kuttan
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D020838:Calendula / Q000737:chemistry*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D035264:Flowers / Q000737:chemistry*; D020869:Gene Expression Profiling; D006801:Humans; D008175:Lung Neoplasms / Q000517:prevention & control* / Q000556:secondary; D008297:Male; D008546:Melanoma, Experimental / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D016207:Cytokines; D010936:Plant Extracts; D012333:RNA, Messenger; D005723:gamma-Glutamyltransferase