Inhibitory effect of a mixture containing ascorbic acid, lysine, proline and green tea extract on critical parameters in angiogenesis

Roomi, M. Waheed; Roomi, Nusrath; Ivanov, Vadim; Kalinovsky, Tatiana; Niedzwiecki, Aleksandra; Rath, Matthias

doi:10.3892/or.14.4.807

Cited by 35 publications

(40 citation statements)

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“…It also exhibited a broad spectrum of anti-tumor activity against a number of cancer cell lines, including inhibition of cell proliferation, cell invasion, anti-metastatic potential, inhibition of angiogenesis and pro-apoptotic effects against a number of human cancer cell lines in vitro and in vivo (15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

Comparative effects of EGCG, green tea and a nutrient mixture on the patterns of MMP-2 and MMP-9 expression in cancer cell lines

Roomi

Monterrey²,

Kalinovsky³

et al. 2010

Oncol Rep

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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 (SKHep-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 dosedependent 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.

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Section: Introductionmentioning

confidence: 99%

Comparative effects of EGCG, green tea and a nutrient mixture on the patterns of MMP-2 and MMP-9 expression in cancer cell lines

Roomi

Monterrey²,

Kalinovsky³

et al. 2010

Oncol Rep

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“…Moreover, disrupted apoptosis contributes to drug resistance of tumor cells, which has become a significant obstacle for the successful management of patients with malignant tumors, including OS (18). The growing amount of evidence from studies on tumor cell cultures and animal tumor models demonstrates that a large number of natural products from the diet can sensitize tumor cells to anti-cancer therapies (19,20). For cancer prevention and chemotherapy, plant-derived natural products are an invaluable treasure and worthy to be further explored.…”

Section: Discussionmentioning

confidence: 99%

“…Cell viability was assessed by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) colorimetric assay. The cells were treated with quercetin at various final concentrations (20,40, 80, 160, 240 and 320 µM, respectively), and the vehicle control cells treated with 0.5% DMSO for 48 h. In some experiments, cells were treated with 160 µM of quercetin for different periods of time. After treatment, 10 µl MTT [5 mg/ml in phosphate buffered saline (PBS)] were added to each well, and the samples were incubated at 37˚C for 4 h. The purple-blue MTT formazan precipitate was dissolved in 100 µl DMSO and cells were shaken for 10 min.…”

Section: Quercetinmentioning

confidence: 99%

Quercetin-mediated apoptosis via activation of the mitochondrial-dependent pathway in MG-63 osteosarcoma cells

2011

Mol Med Report

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Abstract. Quercetin (a natural polyphenolic compound) is a polyphenolic flavonoid compound found in a variety of plants. It has been demonstrated to exert cytostatic activity against a variety of human cancer cell lines, including the human osteosarcoma cell line, MG-63. However, its effects on osteosarcoma cell apoptosis are still undefined. The present study was undertaken to examine the effect of quercetin on cell viability, apoptosis and mitochondrial membrane potential, and to determine the molecular mechanism of quercetininduced apoptosis by investigating the expression of Bcl-2 family proteins (Bcl-2, Bax), cytochrome C, caspase-9 and caspase-3 in MG-63 cells. We found that quercetin suppressed the viability of MG-63 cells in a dose-and time-dependent manner. Furthermore, we observed that quercetin induced the loss of mitochondrial membrane potential, upregulated the expression of the proapoptotic proteins, Bax and cytochrome C, and activated caspase-9 and caspase-3, and downregulated the expression of antiapoptotic protein, Bcl-2. These data suggest that quercetin may induce apoptosis via the mitochondrial-dependent pathway in MG-63 cells. IntroductionOsteosarcoma (OS) is the third most common cancer in childhood and adolescents, and the most common primary malignant bone tumor (1). With the development of new chemotherapy protocols, surgical techniques and radiological staging, the 5-year survival and cure rates have increased to 60-80% in patients with localized disease (2). However, major problems associated with chemotherapy still remain, particularly the frequent development of drug resistance (3). Moreover, chemotherapy may induce DNA mutations in normal cells. Hence the challenge of seeking new therapeutic approaches that can further improve the efficiency and alleviate the adverse effects is clear and urgent (4). Epidemiological studies have shown that regular consumption of tea, vegetables and fruits is associated with reduced risk of cancer (5). Quercetin with a molecular formula of C 15 H 10 O 7 (Fig. 1), is an abundant flavonoid in tea, fruits and vegetables (6). Quercetin has been shown to induce cell death by apoptosis in many human cancer cell lines, such as hepatoma, oral, leukemia, lung and colon cancer cell lines (7,8).Apoptotic cell death is an innate cellular response to eliminate abnormal or redundant cells in mammals and hence is crucial for mammal development and tissue homeostasis (9). The disturbed regulation of this vital process represents a major causative factor in the pathogenesis of cancers, including OS (10,11). The mitochondrial-dependent pathway is one of the apoptotic pathways in mammalian cells. Mitochondrial membrane permeabilization, accompanied by the collapse of electrochemical gradient across the mitochondrial membrane causes the release of catabolic hydrolases and activators of such enzymes (including those of caspases) from the mitochondria, leading to cell apoptosis (12,13). Bcl-2 family proteins serve as critical regulators of this pathway through their influe...

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“…For example, ascorbic acid and the amino acids lysine and proline are critical to proper ECM formation and structural integrity by ensuring synthesis and hydroxylation of collagen fibers (Roomi et al, 2005). Lysine possesses an additional role in maintaining proper collagen formation by inhibiting proteolysis (Rath & Pauling, 1992).…”

Section: Discussionmentioning

confidence: 99%

The Anti-Cancer Effect of a Novel Nutrient Mixture by Inhibiting MMPs Expression, Invasion and Inducing Apoptosis in Chondrosarcoma Cell Line SW-1353

Roomi¹,

Roomi²,

Bhanap³

et al. 2012

CCO

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Chondrosarcoma, a malignant tumor of cartilaginous origin is the most frequent adult primary bone cancers. Surgery is the main treatment option because chondrosarcoma typically does not respond to radiation and chemotherapy. Cancer mortality usually results from the local and distant metastasis. A nutrient mixture containing ascorbic acid, lysine, proline, green tea extract, was tested on chondrosarcoma cells SW-1353 for viability, matrix metalloproteinase expression, Matrigel invasion, morphology and apoptosis. The SW-1353 cells were grown in appropriate media and treated with the nutrient mixture at 10, 50, 100, 500 and 1000 µg/ml concentrations. Cells were also treated with PMA (100 ng/ml) for MMP-9 stimulation. Cell proliferation was carried out by MTT assay, MMPs by zymography, invasion through Matrigel. Morphology and apoptosis were also conducted. The nutrient mixture did not exhibit toxicity at 100 µg/ml, but showed 40% inhibition at 1000 µg/ml. Zymography demonstrated two bands, for MMP-2 and MMP-9. PMA treatment further enhanced MMP-9 expression. The nutrient mixture inhibited expression of both MMPs in a dose dependent manner. Matrigel invasion was reduced by 40%, 70%, 88% and 100% at 50, 100, 500 and 1000 µg/ml respectively. The nutrient mixture induced slight apoptosis at 250 µg/ml, moderate at 500 µg/ml and significant at 1000 µg/ml concentrations. Morphology showed slight changes at the highest concentrations. The nutrient mixture significantly inhibited all the important hallmarks for cancer progression, suggesting that it has a possibility for exploration as a significant therapeutic entity in chondrosarcoma.

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Inhibitory effect of a mixture containing ascorbic acid, lysine, proline and green tea extract on critical parameters in angiogenesis

Cited by 35 publications

References 0 publications

Comparative effects of EGCG, green tea and a nutrient mixture on the patterns of MMP-2 and MMP-9 expression in cancer cell lines

Comparative effects of EGCG, green tea and a nutrient mixture on the patterns of MMP-2 and MMP-9 expression in cancer cell lines

Quercetin-mediated apoptosis via activation of the mitochondrial-dependent pathway in MG-63 osteosarcoma cells

The Anti-Cancer Effect of a Novel Nutrient Mixture by Inhibiting MMPs Expression, Invasion and Inducing Apoptosis in Chondrosarcoma Cell Line SW-1353

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