title: In vivo and in vitro antitumor effect of a unique nutrient mixture on lung cancer cell line A-549.
abstract: The high incidence of lung cancer and ineffective toxic action of current mono and doublet chemotherapy approaches result in poor patient survival. Further, matrix metalloproteinases (MMPs) are implicated in neoplastic invasion and metastasis. Based on this, the authors investigated the effect of a dietary micronutrient mixture (NM) containing lysine, proline, arginine, ascorbic acid, and green tea extract on the tumor growth of human lung carcinoma cell A-549 xenografts in athymic nude mice. Additionally, the authors tested the in vitro antitumor effect of NM on lung carcinoma A-549 cells by measuring cell proliferation by MTT assay, MMP-2 and -9 secretion by gelatinase zymography, and cell invasion through Matrigel. Nutrient supplementation strongly suppressed the growth of tumors without adverse effects in nude mice; tumor weight was reduced by 44% (P = .0001) and tumor burden was reduced by 47% (P < .0001) with supplementation. Zymography demonstrated in vitro secretion of MMP-2 by uninduced human lung carcinoma cells and both MMP-2 and -9 by phorbol 12-mysristate 13-acetate (PMA) (200 ng/mL)-treated cells. NM inhibited the secretion of both MMPs in a dose-dependent fashion, with virtual total inhibition at 500 microg/mL concentration. The invasion of human lung carcinoma cells through Matrigel was significantly reduced at 100 microg/mL (64%) and totally inhibited at 500 microg/mL concentration of NM (P = .01). Suppression of lung tumor growth in nude mice and inhibition of MMP secretion and Matrigel invasion suggest NM may act as an anticancer agent and as such warrants further investigation.
authors.affiliation: Dr. Rath Research Institute, Cancer Division, Santa Clara, California 95050, USA.
authors.forename: M
authors.initials: M
authors.lastname: Waheed 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: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D028241:Camellia sinensis; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007797:Laminin; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008239:Lysine / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D010936:Plant Extracts / Q000494:pharmacology; D011392:Proline / Q000494:pharmacology; D011509:Proteoglycans
chemical_list: D004338:Drug Combinations; D007797:Laminin; D010936:Plant Extracts; D011509:Proteoglycans; C465546:green tea extract AR25; C059485:matrigel; D003094:Collagen; D011392:Proline; D008239:Lysine; D001205:Ascorbic Acid