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Inhibitory Effects of a Nutrient Mixture on Human Testicular Cancer Cell Line NT 2/DT Matrigel Invasion and MMP Activity

M.W. Roomi, V. Ivanov, T. Kalinovsky, A. Niedzwiecki, M. Rath
Medical Oncology 2007, 24(2): 183-188

Abstract:
Current treatment of testicular cancer is associated with secondary malignancy, infertility, and cytotoxicity. Based on reported antimetastatic potential, we investigated the effect of a nutrient mixture (NM) containing lysine, proline, arginine, ascorbic acid, and green tea extract on human testis cancer cell line NT 2/DT by measuring cell proliferation / cytotoxicity, modulation of MMP-2 and MMP-9 secretion, and cancer cell invasive potential. Human testis cancer cells NT 2/DT (ATCC) were grown in DME medium. At near confluence, the cells were treated with NM dissolved in media and tested in 0, 10, 50, and 100 μg/mL in triplicate at each dose.

Cells were also treated with PMA 200 ng/mL to study enhanced secretion of MMP-9. Cell proliferation / cytotoxicity was evaluated by MTT assay, MMP activity by gelatinase zymography, and invasion through Matrigel. The nutrient mixture showed no significant effect on testis cancer cell growth. Zymography demonstrated secretion of MMP-2 by untreated human testis cancer cells and MMP-9 with PMA induction. NM inhibited secretion of both MMPs in a dose-dependent fashion with virtual total inhibition of MMP-9 at 100 μg/mL. Invasion of human testis cancer cells through Matrigel was reduced by 84% at 50 μg/mL and at 100 μg/mL (p = 0.004). NM significantly inhibited MMP secretion and matrix invasion in testicular cancer cells without toxic effect, indicating potential as an anticancer agent.

Key Words:
Testicular cancer, MMPs, Matrigel invasion, nutrients, green tea extract, ascorbic acid, lysine

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