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

  • Authors:
    • M. Waheed Roomi
    • Nusrath Roomi
    • Vadim Ivanov
    • Tatiana Kalinovsky
    • Aleksandra Niedzwiecki
    • Matthias Rath
  • View Affiliations

  • Published online on: October 1, 2005     https://doi.org/10.3892/or.14.4.807
  • Pages: 807-815
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Abstract

Degradation of extracellular matrix (ECM) is a hallmark of tumor invasion, metastasis and angiogenesis. Based on the Rath multitargeted approach to cancer using natural substances to control ECM stability and enhancing its strength, we developed a novel formulation (NM) of lysine, proline, ascorbic acid and green tea extract that has shown significant anti-cancer activity against a number of cancer cell lines. The aim of the present study was to determine whether NM exhibits anti-angiogenic and anti-metastatic effects using in vitro and in vivo experimental models. Angiogenesis was measured using a chorioallantoic membrane (CAM) assay in chick embryos and bFGF-induced vessel growth in C57BL/6J female mice. To determine the in vivo effect of NM on the tumor xenograft growth, male nude mice were inoculated with 3x106 MNNG-HOS cells. Control mice were fed a mouse chow diet, while the test group was fed a mouse chow diet supplemented with 0.5% NM for 4 weeks. In vitro studies on cell proliferation (MTT assay), MMP expression (zymography) and Matrigel invasion were conducted on human osteosarcoma U2OS, maintained in McCoy medium, supplemented with 10% FBS, penicillin and streptomycin in 24-well tissue culture plates and tested with NM at 0, 10, 50, 100, 500, and 1000 µg/ml in triplicate at each dose. NM at 250 µg/ml caused a significant (p<0.05) reduction in bFGF-induced angiogenesis in CAM. NM inhibited tumor growth of osteosarcoma MNNG-HOS cell xenografts in nude mice by 53%; furthermore, tumors in NM-treated mice were less vascular and expressed lower levels of VEGF and MMP-9 immunohistochemically than tumors in the control group. In addition, NM exhibited a dose-dependent inhibition of osteosarcoma U2OS cell proliferation (up to 60% at 1000 µg/ml), MMP-2 and -9 expression (with virtual total inhibition at 500 µg/ml NM), and invasion through Matrigel (with total inhibition at 100 µg/ml NM). Moreover, NM decreased U2OS cell expression of VEGF, angiopoietin-2, bFGF, PDGF and TGFβ-1. These results together with our earlier findings suggest that NM is a relatively non-toxic formulation, which inhibits growth, invasion, metastasis, and angiogenesis of tumor cells.

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October 2005
Volume 14 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Roomi MW, Roomi N, Ivanov V, Kalinovsky T, Niedzwiecki A and Rath M: Inhibitory effect of a mixture containing ascorbic acid, lysine, proline and green tea extract on critical parameters in angiogenesis. Oncol Rep 14: 807-815, 2005
APA
Roomi, M.W., Roomi, N., Ivanov, V., Kalinovsky, T., Niedzwiecki, A., & Rath, M. (2005). Inhibitory effect of a mixture containing ascorbic acid, lysine, proline and green tea extract on critical parameters in angiogenesis. Oncology Reports, 14, 807-815. https://doi.org/10.3892/or.14.4.807
MLA
Roomi, M. W., Roomi, N., Ivanov, V., Kalinovsky, T., Niedzwiecki, A., Rath, M."Inhibitory effect of a mixture containing ascorbic acid, lysine, proline and green tea extract on critical parameters in angiogenesis". Oncology Reports 14.4 (2005): 807-815.
Chicago
Roomi, M. W., Roomi, N., Ivanov, V., Kalinovsky, T., Niedzwiecki, A., Rath, M."Inhibitory effect of a mixture containing ascorbic acid, lysine, proline and green tea extract on critical parameters in angiogenesis". Oncology Reports 14, no. 4 (2005): 807-815. https://doi.org/10.3892/or.14.4.807