Amentoflavone inhibits experimental tumor metastasis through a regulatory mechanism involving MMP-2, MMP-9, prolyl hydroxylase, lysyl oxidase, VEGF, ERK-1, ERK-2, STAT-1, NM23 and cytokines in lung tissues of C57BL/6 mice.
Amentoflavone has been shown to inhibit tumor metastasis in vivo, but its mechanism of action remains unclear. Here, C57BL/6 mice were injected once with B16F-10 melanoma cells via tail vein followed by amentoflavone treatment (50 mg/kg BW) for 10 consecutive days. Twenty-one days after tumor injection, animals were euthanized, and tumor metastasis was found to confine in the lungs. As compared with the tumor controls, amentoflavone treatment significantly lowered the number of lung nodules (p<0.001). Amentoflavone treatment markedly decreased the mRNA expression of MMP-2, MMP-9, prolyl hydroxylase, lysyl oxidase, VEGF, ERK-1, ERK-2, TNF-alpha, IL-1beta, IL-6, and GM-CSF in lung tissues. However, amentoflavone treatment increased the mRNA expression of STAT-1 and nm23 in lung tissues. Also in vitro studies indicate that amentoflavone treatment inhibits tumor cell invasion and migration. These results show that amentoflavone treatment reduces experimental tumor metastasis and suggest that such an action is associated with attenuation of tumor invasion, proliferation and angiogenesis.
Guruvayoorappan
Chandrasekaran
C
Department of Immunology, Amala Cancer Research Centre, Amala Nagar, Kerala, India.
Kuttan
Girija
G
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D044946:Biflavonoids / Q000008:administration & dosage / Q000627:therapeutic use*; D016207:Cytokines / Q000502:physiology*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology / Q000556:secondary*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000502:physiology; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology / Q000556:secondary*; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology; D048052:Mitogen-Activated Protein Kinase 3 / Q000502:physiology; D054778:NM23 Nucleoside Diphosphate Kinases / Q000502:physiology; D011393:Procollagen-Proline Dioxygenase / Q000502:physiology; D008249:Protein-Lysine 6-Oxidase / Q000502:physiology; D050794:STAT1 Transcription Factor / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
D000972:Antineoplastic Agents, Phytogenic; D044946:Biflavonoids; D016207:Cytokines; D054778:NM23 Nucleoside Diphosphate Kinases; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D042461:Vascular Endothelial Growth Factor A; C011164:amentoflavone; D011393:Procollagen-Proline Dioxygenase; D008249:Protein-Lysine 6-Oxidase; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020778:Matrix Metalloproteinase 2