M.W. Roomi, V. Ivanov, T. Kalinovsky, A. Niedzwiecki, M. Rath
Medical Oncology 2007, 24(2): 231-238
Standard multimodality therapy of gliomas is associated with poor patient survival and significant toxicity. Abnormal expression of matrix metalloproteinases (MMPS) is associated with tumor growth and invasion. We investigated the effect of a combination of natural compounds (NM), primarily composed of lysine, proline, ascorbic acid and green tea extract in vitro on glioma cell line A-172, by measuring MMP secretion, invasion through Matrigel, and cell proliferation. Glioma cells A-172 (ATCC) were grown in modified Dulbecco’s Eagle medium with10% fetal bovine serum and antibiotics and treated with NM at 0, 10, 50, 100, 500 and 1000 µg/ml concentration in triplicate at each dose. Cell proliferation was assayed by MTT, MMP secretion by zymography, invasion through Matrigel, and morphology by H&E staining.
Zymography showed one band corresponding to MMP-2, which was inhibited by NM in a dose dependent fashion, with virtual total inhibition at 500-µg/ml concentration. Invasion through Matrigel was completely inhibited at 1000 µg/ml NM. NM was not toxic to glioma cell line A-172 at lower concentrations and exhibited toxicity of 50 % over the control at 1000 µg/ml. These results are significant as the nutrient mixture significantly inhibited MMP secretion and invasion-important parameters for cancer prevention without toxic effects, suggesting NM as a potential therapeutic agent for treatment of glioma.
Glioma, MMPs, Matrigel invasion, nutrients