M.W. Roomi, N.W. Roomi, T. Kalinovsky, M. Rath, A. Niedzwiecki
Integrative Cancer Therapies 2009; 8(2): 168-176
Head and neck squamous cell carcinomas (HNSCC) are known for their aggressive growth and propensity to metastasize. We investigated the effect of a novel nutrient mixture (NM) containing ascorbic acid, lysine, proline, and green tea extract on human HNSCC cell line FaDu in vivo and in vitro. Athymic male nude mice (n=12) were inoculated with 3 x 106 FaDu cells subcutaneously and randomly divided into two groups; group A was fed a regular diet and group B a regular diet supplemented with 0.5% NM. Four weeks later, the mice were sacrificed and their tumors were excised, weighted and processed for histology.
In vitro, FaDu cells were cultured in DME and exposed to NM at 0-1000 μg/ml in triplicate. Cell proliferation was assessed by MTT assay, MMP secretion by gelatinase zymography, invasion through Matrigel, apoptosis by live-green caspases, and cell morphology by H&E staining. NM inhibited the growth of tumors by 55% (p =0.0002) and exhibited dose dependent toxicity on FaDu cells in vitro, with 53% (p=0.0003) at 1000 μg/ml NM. Zymography revealed MMP-2 and phorbol 12-myristate 13-acetate -induced MMP-9 secretion. NM inhibited secretion of both MMPs in a dose-dependent manner, with virtual total inhibition at 1000 µg/ml. NM significantly inhibited FaDu invasion through Matrigel with total block at 1000 µg/ml. NM induced dose-dependent apoptosis. In conclusion, NM has therapeutic potential in treatment of HNSCC by significantly suppressing tumor growth and significantly inhibiting MMP secretion and invasion of HNSCC cells in vitro.
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