title: Repression of matrix metalloproteinases and inhibition of cell invasion by a nutrient mixture, containing ascorbic acid, lysine, proline, and green tea extract on human Fanconi anemia fibroblast cell lines.
abstract: OBJECTIVE
  Fanconi Anemia, an autosomal recessive disorder, is characterized by chromosomal abnormality leading to birth defects, progressive bone marrow failure, and a high probability of developing malignancy at an early age. Head and neck squamous cell carcinoma and myeloid leukemia are the major causes of cancer related morbidity and mortality in Fanconi anemia patients.
  
  
  METHODS
  We investigated the effect of a nutrient mixture on Fanconi Anemia human fibroblast cell lines FA-A:PD20 and FA-A:PD220 on matrix metalloproteinase expression, invasion, cell proliferation, morphology and apoptosis. The cell lines were grown in a modified Dulbecco's Eagle medium and at near confluence were treated with the nutrient mixture at increasing doses: 0; 10; 50; 100; 500; 1000 µg/ml. The cells were also treated with PMA to induce MMP-9 expression.
  
  
  RESULTS
  Zymography demonstrated MMP-2 and PMA-induced MMP-9 activity. The nutrient mixture inhibited expression of both, MMP-2 and MMP-9, in a dose dependent manner with virtually total inhibition observed at 500 µg/ml. Matrigel invasion was inhibited in both cells lines; with 100% inhibition for FA-A:PD20 at 500 µg/ml and 100% inhibition of FA-A:P220 cells at 100 µg/ml. H&E staining did not indicate any change in cell morphology and causes apoptosis at higher doses.
  
  
  CONCLUSIONS
  Our data demonstrated that the nutrient mixture inhibited matrix metalloproteinase expression, invasion and induced apoptosis, the important parameters for cancer prevention. The results suggest that the nutrient mixture may have therapeutic potential in Fanconi Anemia associated neoplasia.
authors.affiliation: Dr. Rath Research Institute, Cancer Division, Santa Clara, CA-95050, USA.
authors.forename: M W
authors.initials: MW
authors.lastname: Roomi
authors.forename: N W
authors.initials: NW
authors.lastname: Roomi
authors.forename: B
authors.initials: B
authors.lastname: Bhanap
authors.forename: A
authors.initials: A
authors.lastname: Niedzwiecki
authors.forename: M
authors.initials: M
authors.lastname: Rath
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001120:Arginine / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D005199:Fanconi Anemia / Q000188:drug therapy*; D006801:Humans; D008239:Lysine / Q000494:pharmacology; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000187:drug effects; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D011392:Proline / Q000494:pharmacology; D013662:Tea
chemical_list: D000975:Antioxidants; D013662:Tea; D001120:Arginine; D011392:Proline; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D008239:Lysine; D001205:Ascorbic Acid