title: Inhibition of glioma cell line A-172 MMP activity and cell invasion in vitro by a nutrient mixture.
abstract: Standard multimodality therapy of gliomas is associated with poor patient survival and significant toxicity. Abnormal expression of matrix metalloproteinases is associated with tumor growth and invasion. Based on reported antitumor properties, we investigated the effect of a combination of natural compounds (NM), primarily composed of lysine, proline, ascorbic acid, and green tea extract in vitro on glioma cell line A-172, by measuring MMP secretion, invasion through Matrigel, and cell proliferation. Glioma cells A-172 (ATCC) were grown in modified Dulbecco's Eagle medium with 10% fetal bovine serum and antibiotics and treated with NM at 0, 10, 50, 100, 500, and 1000 microg/mL concentration in triplicate at each dose. Cell proliferation was assayed by MTT, MMP secretion by zymography, invasion through Matrigel, and morphology by H&E staining. Zymography showed one band corresponding to MMP-2, which was inhibited by NM in a dose-dependent fashion, with virtual total inhibition at 500-microg/mL concentration. Invasion through Matrigel was completely inhibited at 1000 microg/mL NM. NM was not toxic to glioma cell line A-172 at lower concentrations and exhibited toxicity of 50% over the control at 1000 microg/mL. NM significantly inhibited MMP secretion and invasion-important parameters for cancer prevention, suggesting a possible therapeutic role.
authors.affiliation: Oncology Division, Dr. Rath Research Institute, 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: D000111:Acetylcysteine / Q000494:pharmacology / Q000627:therapeutic use; D000596:Amino Acids / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001120:Arginine / Q000494:pharmacology / Q000627:therapeutic use; D001205:Ascorbic Acid / Q000494:pharmacology / Q000627:therapeutic use; D028241:Camellia sinensis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D003094:Collagen / Q000378:metabolism; D004338:Drug Combinations; D005910:Glioma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D006801:Humans; D007797:Laminin / Q000378:metabolism; D008239:Lysine / Q000494:pharmacology / Q000627:therapeutic use; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D011392:Proline / Q000494:pharmacology / Q000627:therapeutic use; D011509:Proteoglycans / Q000378:metabolism
chemical_list: D000596:Amino Acids; D000970:Antineoplastic Agents; D004338:Drug Combinations; D007797:Laminin; D061965:Matrix Metalloproteinase Inhibitors; D010936:Plant Extracts; D011509:Proteoglycans; C465546:green tea extract AR25; C059485:matrigel; D003094:Collagen; D001120:Arginine; D011392:Proline; D020782:Matrix Metalloproteinases; D008239:Lysine; D001205:Ascorbic Acid; D000111:Acetylcysteine