title: Inhibition of malignant mesothelioma cell matrix metalloproteinase production and invasion by a novel nutrient mixture.
abstract: Malignant mesothelioma (MM), an asbestos-associated cancer with no known cure, is a highly aggressive tumor causing profound morbidity and nearly universal mortality. Extracellular matrix (ECM) matrix metalloproteinases (MMPs) produced by tumor and stromal cells play a key role in tumor invasion and metastasis. Prevention of ECM degradation by MMP inhibition has been shown to be a promising therapeutic approach to inhibition of cancer development. Based on reported anticancer properties, the authors investigated the effect of a mixture (NM) containing lysine, proline, ascorbic acid, and green tea extract on MM cell line MSTO-211 H proliferation (by [MTT] [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay), MMP secretion (by gelatinase zymography), invasion (through Matrigel), and morphology (by hematoxylin and eosin [H&E] staining). MMP-2 and phorbol 12-myristate 13-acetate (PMA)-induced MMP-9 secretion were inhibited by NM in a dose-dependent fashion, with virtual total inhibition at 500 microg/ml NM. Invasion through Matrigel was inhibited at 50, 100, and 500 microg/ml by 27%, 36%, and 100%, respectively. NM was not toxic to the MM cell line, and H&E staining did not indicate any changes at and below 100 microg/ml concentration. In conclusion, NM significantly inhibited MM cell MMP secretion and invasion-both important parameters for cancer prevention, suggesting NM is an effective treatment strategy for MM.
authors.affiliation: Dr. Rath Research Institute, Cancer Division, Santa Clara, California, 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: D001205:Ascorbic Acid / Q000494:pharmacology / Q000627:therapeutic use; D028241:Camellia sinensis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004338:Drug Combinations; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008239:Lysine / Q000494:pharmacology / Q000627:therapeutic use; D020782:Matrix Metalloproteinases / Q000187:drug effects* / Q000378:metabolism; D008654:Mesothelioma / Q000188:drug therapy* / Q000473:pathology; D009361:Neoplasm Invasiveness; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D011392:Proline / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D004338:Drug Combinations; D010936:Plant Extracts; D011392:Proline; D020782:Matrix Metalloproteinases; D008239:Lysine; D001205:Ascorbic Acid