Cancer

Failure Of Mmp-9 Dimer Induction By Pma In Normal Human Cell Lines

M.W. Roomi, T. Kalinovsky, M. Rath and A. Niedzwiecki
Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050
Oncology Letters 2015; 9(6), 2871-2873

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. Though there is little research on MMP-9 dimers, some studies have shown the dimer to be associated with more aggressive tumor progression as cell migration depends upon MMP-9 dimer, not the monomer.

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Effect of a nutrient mixture on matrix metalloproteinase-9 dimers in various human cancer cell lines

M.W. Roomi, T. Kalinovsky, M. Rath, A. Niedzwiecki 
Dr. Rath Research Institute, Santa Clara, CA
International Journal of Oncology 2014, 44: 986-992

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. Though 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 by 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. 

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Comparative Effects of EGCG, Green Tea, and a Nutrient Mixture on the Patterns of MMP-2 and MMP-9 Expression in Cancer Cell Lines

M.W. Roomi, J.C. Monterrey, T. Kalinovsky, M. Rath and A. Niedzwiecki
Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050

Onc Rep 2010, 24: 747-757

Abstract
Type IV collagenase matrix metalloproteinases (MMPs), especially MMP-2 and MMP-9, have been found to promote invasion and metastasis of malignant tumors. Extracellular matrix (ECM) degradation by MMPs and increased expression of MMPs in cancer cells and tumor microvascular endothelial cells make MMPs an attractive target for cancer. Focused on a common pathomechanism of cancer growth and invasion, the disintegration of connective tissue, we used natural approaches to increase the integrity and strength of connective tissues. Utilizing the principle of nutrition synergy, we developed a novel micronutrient mixture (NM) containing lysine, proline, ascorbic acid, and green tea extract. This study evaluates the potency of the components EGCG and green tea extract independently compared to that of NM on modulation of patterns of MMP-2 and MMP-9 expression in four cancer cell lines expressing MMP-2, MMP-9 or both. Human fibrosarcoma (HT-1080), hepatocellular carcinoma (SK-Hep-1), glioblastoma (T-98G), uterine leiomyosarcoma (SK-UT-1) cell lines were obtained from ATCC and grown in minimum essential medium (MEM) supplemented with 10% FBS, penicillin (100 U/ml) and streptomycin (100 mg/ml) in 24-well tissue culture plates. At near confluence, the cells were treated with agents dissolved in media and tested at concentrations indicated in triplicate at each dose. Cells were also treated with PMA 100 ng/ml to study enhanced expression of MMP-9. MMP expression was assessed by gelatinase zymography, Fibrosarcoma and hepatocellular carcinoma cells expressed both MMP-2 and MMP-9. Glioblastoma cells expressed MMP-2 and PMA treatment induced MMP-9 expression. Uterine leimyosarcoma cells expressed no MMPs but PMA induced MMP-9. NM was the most potent dose-dependent inhibitor of MMPs, followed by green tea extract and EGCG. In conclusion, these results suggest the enhanced efficacy of nutrients working in synergy to modulate complex pathways such as MMP expression.

Key Words:
EGCG, green tea, nutrient mixture, MMP-2, MMP-9

 

Attachments:
Synergy_OR.pdf [ ] 482 Kb

 

Inhibition of Invasion and MMPs by a Nutrient Mixture in Human Cancer Cell Lines: A Correlation Study

M.W. Roomi, J.C. Monterrey, T. Kalinovsky, M. Rath, and A. Niedzwiecki
Exp Oncol 2010, 32:243-248

Aim
Matrix metalloproteinase (MMP)-2 and -9 secretion is elevated in various human cancers and their elevated expression has been associated with poor prognosis due to associated increased cancer cell invasion and metastasis. The aim of this study was to examine the correlation between in vitro MMP-2 and MMP-9 secretion and Matrigel invasion in 42 different human cancer cell lines (selected on the basis of organ malignancies) treated with a nutrient mixture (NM).

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Distinct patterns of matrix metalloproteinase-2 and -9 expression in normal human cell lines

M.W. Roomi, J.C. Monterrey, T. Kalinovsky, M. Rath, A. Niedzwiecki
Oncology Reports 2009; 21(3): 821-826

Invasion of surrounding tissues by malignant cells is a complex process mediated by the matrix degrading enzymes. In many solid tumors, the expression of MMPs, especially MMP-2 and MMP-9, is higher in stromal cells than in the tumor cells, suggesting stromal cells as the major source of these enzymes. Cytokines and signal transduction pathways, including those activated by phorbol 12-myristate 13-acetate (PMA), regulate the expression of MMPs. The aim of this study was to examine the pattern of MMP-2 and MMP-9 expression in human normal cells and in PMA-treated cells to determine if specific patterns of expression were associated with tissues of different origin.

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