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Anticancer Effects of a Specific Mixture of Nutrients in Multidrug Resistant Human Uterine Sarcoma Cell Line MES-SA/Dx5 and in Drug Sensitive MES-SA Cell Line

 

M.W. Roomi, T. Kalinovsky, N.W. Roomi, M. Rath and A. Niedzwiecki
Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050
Oncology Reports 2011, 27: 17-27

Abstract:
A specific nutrient mixture containing lysine, proline, ascorbic acid and green tea extract (NM) has demonstrated a broad spectrum of antitumor activity against a number of cancer cell lines. In this study, our main objective was to investigate the comparative effects of NM on anticancer parameters such as cytotoxicity, MMP secretion, and Matrigel invasion in the human uterine sarcoma drug-resistant MES-SA/Dx5 and drug sensitive drug-sensitive MES-SA cell lines. In addition we studied the effect 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&E, and Pgp expression by Western blot and immunodetection using FITC-conjugated antibody and rhodamine-123 accumulation and efflux assays. NM exhibited antiproliferative effect on MES-SA/Dx5, by 20% at 50 and 100 μg/ml and by 36%, 40% and 48% at 250, 500 and 1000 μg/ml, respectively. In contrast, NM treatment of MES-SA cells resulted in significantly increased cytotoxicity: 40%, 46%, 65% and 72% at 50, 100, 500 and 1000 μg/ml, respectively. In both cell lines, zymography demonstrated a band corresponding to MMP-2 in normal cells and MMP-9 with PMA treatment. Both MMPs showed dose-response inhibition by NM. NM treatment also showed diminished dose-dependent Pgp expression by MES-SA/Dx5 cell line by Western blot and by immunodetection, whereas MES-SA did not exhibit Pgp by Western blot or by immunostaining. NM enhanced the accumulation and efflux of Pgp substrate Rh-123 in MES-SA/Dx5 uterine sarcoma cell line but not in the drug-sensitive cell line MES-SA. In conclusion, NM demonstrated potent anticancer effects in both the drug-resistant and sensitive cell lines and modulated Pgp, suggesting its potential therapeutic effect in drug resistant, as well as sensitive cancers.

Keywords
nutrients; multidrug resistant uterine sarcoma; MES-SA; MES-SA/Dx5; p-glycoprotein; MMPs; cytotoxicity; Matrigel invasion

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