title: 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.
abstract: A specific nutrient mixture (NM) containing lysine, proline, ascorbic acid             and green tea extract 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,             matrix metalloproteinase (MMP) secretion and Matrigel invasion in the human uterine             sarcoma drug-resistant MES-SA/Dx5 and the drug-sensitive MES-SA cell lines. In             addition 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&E and Pgp expression by Western             blot analysis and immunodetection using FITC-conjugated antibody and rhodamine 123             (Rh123) accumulation and efflux assays. NM exhibited antiproliferative effects             on MES-SA/Dx5, by 20% at 50 and 100 µg/ml and by 36, 40 and 48% at 250, 500 and             1,000 µg/ml, respectively. By contrast, NM treatment of MES-SA cells resulted             in significantly increased cytotoxicity: 40, 46, 65 and 72% at 50, 100, 500 and             1,000 µg/ml, respectively. In both cell lines, zymography demonstrated a band             corresponding to MMP-2 in normal cells and MMP-9 with phorbol 12-myristate 13-acetate             treatment. The two MMPs showed dose-response inhibition by NM. As shown by Western             blot analysis and immunodetection, NM treatment resulted in a dose-dependent decrease             in Pgp expression in the MES-SA/Dx5 cell line. The MES-SA cell line does not exhibit             Pgp. NM enhanced the accumulation and efflux of the Pgp substrate, Rh123, in the             MES-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 anticancer             effects in both the drug-resistant and sensitive cell lines and modulates Pgp,             suggesting its potential therapeutic effects in drug-resistant as well as sensitive             cancers.
authors.affiliation: Dr Rath Research Institute, 1260 Memorex Drive, Santa Clara,                     CA 95050, USA.
authors.forename: M W
authors.initials: MW
authors.lastname: Roomi
authors.forename: T
authors.initials: T
authors.lastname: Kalinovsky
authors.forename: N W
authors.initials: NW
authors.lastname: Roomi
authors.forename: M
authors.initials: M
authors.lastname: Rath
authors.forename: A
authors.initials: A
authors.lastname: Niedzwiecki
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D005502:Food; D006801:Humans; D008239:Lysine / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology; D011392:Proline / Q000494:pharmacology; D012509:Sarcoma / Q000378:metabolism* / Q000473:pathology; D013662:Tea; D014594:Uterine Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D010936:Plant Extracts; D013662:Tea; D011392:Proline; D008239:Lysine; D001205:Ascorbic Acid