title: Antitumor effect of nutrient synergy on human osteosarcoma cells U-2OS, MNNG-HOS and Ewing's sarcoma SK-ES.1.
abstract: Current treatment of osteosarcoma is associated with poor prognosis, especially due to the increased risk of developing other cancers with chemotherapy. Therefore, new, safe and effective treatment strategies are needed. We investigated the effect of a unique mixture of nutrients containing lysine, proline, arginine, ascorbic acid, and epigallocatechin gallate (EGCG) on human osteosarcoma cell lines U-2OS, MNNG-HOS, and Ewing's sarcoma SK-ES-1 by measuring: cell proliferation, expression of matrix metalloproteinase-2 (MMP-2), MMP-9, and invasive and angiogenesis potential. Cell proliferation was evaluated by MTT assay, matrix metalloproteinases (MMP) expression by gelatinase zymography, VEGF expression by ELISA, and invasion through Matrigel. Cells were also treated with phorbol 12-myristate 13-acetate (PMA) to study enhanced MMP and VEGF expression. The invasion of osteosarcoma U-2OS and MNNG-HOS cells through Matrigel was significantly reduced in a dose-dependent fashion, with 100% inhibition of invasion of U-2OS cells at 100 microg/ml, and MNNG cells at 50 microg/ml concentration of the synergistically acting nutrient mixture. Ewing's sarcoma SK-ES-1 cells were not invasive. Nutrient synergy (NS) exhibited a dose response antiproliferative effect on osteosarcoma U-2OS cells, reaching 67% at 1000 microg/ml of NS; no significant suppression of cell proliferation was seen with MNNG or Ewing's sarcoma cells. Zymography showed dose-dependent inhibition of MMP secretion by all three cell lines in the presence of NS. VEGF secretion by U-2OS cells was completely blocked at 500 microg/ml of NS. Our results suggest NS is an excellent candidate for therapeutic use in the treatment of osteosarcoma, by inhibiting cancer cell invasion, and secretion of MMPs and VEGF, all critical parameters for cancer control and prevention.
authors.affiliation: Matthias Rath Research, Cancer Division, 1260 Memorex Drive, Santa Clara, CA 95050, USA.
authors.forename: M Waheed
authors.initials: MW
authors.lastname: Roomi
authors.forename: Vadim
authors.initials: V
authors.lastname: Ivanov
authors.forename: Tatiana
authors.initials: T
authors.lastname: Kalinovsky
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Niedzwiecki
authors.forename: Matthias
authors.initials: M
authors.lastname: Rath
mesh_terms: D001120:Arginine / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D001859:Bone Neoplasms / Q000188:drug therapy*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008239:Lysine / Q000494:pharmacology; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D009747:Nutritional Physiological Phenomena; D012516:Osteosarcoma / Q000188:drug therapy*; D011392:Proline / Q000494:pharmacology; D012512:Sarcoma, Ewing / Q000188:drug therapy*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D002392:Catechin; D001120:Arginine; D011392:Proline; C045651:epigallocatechin gallate; D020782:Matrix Metalloproteinases; D008239:Lysine; D013755:Tetradecanoylphorbol Acetate; D001205:Ascorbic Acid