Anticancer effect of lysine, proline, arginine, ascorbic acid and green tea extract on human renal adenocarcinoma...

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.