title: Effect of a nutrient mixture on matrix metalloproteinase-9 dimers in various human cancer cell lines.
abstract: Strong clinical and experimental evidence demonstrates association of elevated levels of matrix metalloproteinase MMP-9 with cancer progression, metastasis and shortened patient survival, as it plays a key role in tumor cell invasion and metastasis by digesting the basement membrane and ECM components. MMP-9 is secreted in both the monomeric and dimeric form. Although there is little research on MMP-9 dimers, some studies have shown the dimer to be associated with more aggressive tumor progression. Our objective was to study the relative secretion patterns of MMP-9 monomer and dimer in a variety of cancer cell lines and the effect of a nutrient mixture (NM) containing lysine, proline, ascorbic acid and green tea extract on MMP-9 secretion. The cancer cell lines were grown in their respective media, supplemented with 10% FBS, penicillin (100 U/ml) and streptomycin (100 µg/ml) in 24-well tissue culture plates. At near confluence, the cells were treated with NM at 0,10, 50, 100, 500 and 1000 µg/ml. Parallel sets of cultures were treated with PMA (100 ng/ml) for induction of MMP-9. Cell MMP-9 secretion was assayed by gelatinase zymography. MMP-9 dimer secretion patterns of cancer cells fell into different categories. We observed no MMP-9 dimer in prostate DU-145 and PC-3, pancreatic MIA-Pa-Ca2, colon HCT-116, bladder T-24, head and neck FaDu, glioblastoma A-172, T-98 and LN-18 and leukemia HL-60, Jurkat, and Raji cell lines. MMP-dimer secretion only with PMA induction was seen in breast MCF-7 and MDA-MB-231, uterine SK-UT-1, lung A-549, tongue SC-25, melanoma A2058, osteosarcoma U-2OS, rhabdomyosarcoma, fibrosarcoma HT-1080, chondrosarcoma SW-1350 and liposarcoma SW-872. Cervical HeLa and DoTc 2 4510, renal 786-0 and HCC SK-Hep-1 cells exhibited MMP-9 dimer without PMA treatment and increased secretion with PMA treatment. Sarcomas had the highest levels of MMP-9 monomer and dimer with and without PMA among these cancer cell lines. Cervical, uterine and male breast cancer cell lines showed the next highest levels of MMP-9, followed by breast cancer cell lines. Melanoma, renal, lung, head and neck and HCC showed lower levels and prostate, glioblastoma, bladder and leukemia cell lines the lowest. NM showed dose-dependent inhibition of MMP-9 monomer and dimer in all cell lines tested. In conclusion, high MMP-9 and dimer secretion levels correlated with the most aggressive cancer cell lines. NM was effective in inhibiting MMP-9 and dimer secretion in all cell lines tested, suggesting its therapeutic potential as an antimetastatic agent.
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.affiliation: Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050, USA.
authors.forename: T
authors.initials: T
authors.lastname: Kalinovsky
authors.affiliation: Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050, USA.
authors.forename: M
authors.initials: M
authors.lastname: Rath
authors.affiliation: Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050, USA.
authors.forename: A
authors.initials: A
authors.lastname: Niedzwiecki
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D019281:Dimerization; D018093:Gelatinases / Q000096:biosynthesis / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D008239:Lysine / Q000494:pharmacology; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D011392:Proline / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis
chemical_list: D000975:Antioxidants; D011392:Proline; D014568:Urokinase-Type Plasminogen Activator; D018093:Gelatinases; D020780:Matrix Metalloproteinase 9; D008239:Lysine; D001205:Ascorbic Acid