Anticancer effect of lysine, proline, arginine, ascorbic acid and green tea extract on human renal adenocarcinoma line 786-0.
Five-year survival is limited to 60% in renal cancer patients at diagnosis. Due to the cancer's resistance to conventional treatments and associated high morbidity, we investigated the antimetastatic effects of a specific nutrient mixture (NM) containing lysine, proline, arginine, ascorbic acid and green tea extract on human renal adenocarcinoma cell line 786-0 by measuring: cell proliferation, modulation of MMP-2 and -9 secretion, and cancer cell invasive potential. Human renal cancer cell line 786-0 (ATCC) was grown in RPMI medium in 24-well tissue culture plates. At near confluence, the cells were treated with NM, dissolved in media, and tested at 0, 10, 50, 100, 500 and 1000 microg/ml in triplicate at each dose. Cells were also treated with PMA 200 ng/ml to study enhanced MMP-9 activity. Cell proliferation was evaluated by MTT assay, MMP secretion by gelatinase zymography, and invasion through Matrigel. Zymography demonstrated MMP-2 and MMP-9 secretion by uninduced renal cancer cells with enhanced MMP-9 induced by PMA (200 ng/ml) treatment. NM inhibited the secretion of both MMPs in a dose-dependent fashion with virtual total inhibition of MMP-2 at 500-microg/ml concentration and MMP-9 at 100 microg/ml. The invasion of renal cancer cells through Matrigel was totally inhibited (p=0.0001) by NM at 1000 microg/ml concentration. Our results support a potential role for the nutrient mixture tested in the treatment of renal cell carcinoma, by inhibition of MMP-2 and MMP-9 secretion and invasion.
Roomi
M Waheed
MW
Matthias Rath Research Institute, Cancer Division, Santa Clara, CA 95050, USA.
Ivanov
Vadim
V
Kalinovsky
Tatiana
T
Niedzwiecki
Aleksandra
A
Rath
Matthias
M
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001120:Arginine / Q000008:administration & dosage; D001205:Ascorbic Acid / Q000008:administration & dosage; D028241:Camellia sinensis; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D003094:Collagen; D004338:Drug Combinations; D018093:Gelatinases / Q000378:metabolism; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D007797:Laminin; D008239:Lysine / Q000008:administration & dosage; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D010936:Plant Extracts / Q000008:administration & dosage / Q000627:therapeutic use; D011392:Proline / Q000008:administration & dosage; D011509:Proteoglycans
D004338:Drug Combinations; D007797:Laminin; D010936:Plant Extracts; D011509:Proteoglycans; C465546:green tea extract AR25; C059485:matrigel; D003094:Collagen; D001120:Arginine; D011392:Proline; D018093:Gelatinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008239:Lysine; D001205:Ascorbic Acid