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A specific nutrient mixture (NM) containing lysine, proline, ascorbic acidand green tea extract has demonstrated a broad spectrum of antitumor activityagainst a number of cancer cell lines. In this study, our main objective was toinvestigate the comparative effects of NM on anticancer parameters, such as cytotoxicity,matrix metalloproteinase (MMP) secretion and Matrigel invasion in the human uterinesarcoma drug-resistant MES-SA/Dx5 and the drug-sensitive MES-SA cell lines. Inaddition we studied the effects of NM on P-glycoprotein (Pgp) on these cell lines.Cell proliferation was evaluated by MTT assay, MMPs by gelatinase zymography,invasion through Matrigel, morphology by H&amp;E and Pgp expression by Westernblot analysis and immunodetection using FITC-conjugated antibody and rhodamine 123(Rh123) accumulation and efflux assays. NM exhibited antiproliferative effectson MES-SA/Dx5, by 20% at 50 and 100 µg/ml and by 36, 40 and 48% at 250, 500 and1,000 µg/ml, respectively. By contrast, NM treatment of MES-SA cells resultedin significantly increased cytotoxicity: 40, 46, 65 and 72% at 50, 100, 500 and1,000 µg/ml, respectively. In both cell lines, zymography demonstrated a bandcorresponding to MMP-2 in normal cells and MMP-9 with phorbol 12-myristate 13-acetatetreatment. The two MMPs showed dose-response inhibition by NM. As shown by Westernblot analysis and immunodetection, NM treatment resulted in a dose-dependent decreasein Pgp expression in the MES-SA/Dx5 cell line. The MES-SA cell line does not exhibitPgp. NM enhanced the accumulation and efflux of the Pgp substrate, Rh123, in theMES-SA/Dx5 uterine sarcoma cell line but not in the drug-sensitive cell line,MES-SA. Therefore, it can be concluded that NM demonstrates potent anticancereffects in both the drug-resistant and sensitive cell lines and modulates Pgp,suggesting its potential therapeutic effects in drug-resistant as well as sensitivecancers.

oncology reports

Anticancer effects of a specific mixture of nutrients in the multidrug-resistant human uterine sarcoma MES-SA/Dx5 and the drug-sensitive MES-SA cell lines