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In vitro and in vivo inhibition of human Fanconi anemia-associated head and neck squamous cell carcinoma by a novel nutrient mixture

  • Authors:
    • M. W. Roomi
    • T. Kalinovsky
    • N. W. Roomi
    • A. Niedzwiecki
    • M. Rath

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  • Published online on: September 24, 2012     https://doi.org/10.3892/ijo.2012.1639
  • Pages: 1996-2004

  • Copyright: © Roomi et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Head and neck squamous cell carcinoma (HNSCC) and acute myeloid leukemia are the major causes of mortality and morbidity in Fanconi anemia (FA) patients. The objective of this study was to investigate the antineoplastic activity of a novel antineoplastic nutrient mixture (NM) (containing lysine, proline, ascorbic acid and green tea extract) in human FA-associated HNSCC (FA HNSCC) in vitro and in vivo. The human FA HNSCC cell line, OHSU-974 (Fanconi Anemia Research Fund), was cultured in RPMI medium supplemented with 20% FBS and antibiotics. At near confluence, cells were treated in triplicate with various concentrations of NM: 0, 50, 100, 250, 500 and 1,000 µg/ml. Cells were also treated with phorbol 12-myristate 13-acetate (PMA) to induce matrix metalloproteinase (MMP)-9 activity. Cell proliferation was detected by MTT assay, the secretion of MMPs by gelatinase zymo­graphy, cell invasion through Matrigel, cell migration by a scratch test and morphology by hematoxylin and eosin (H&E) staining. In vivo, athymic male nude mice (n=12) were inoculated with 3x106 OHSU‑974 cells subcutaneously and randomly divided into 2 groups: group A was fed a regular diet and group B a regular diet supplemented with 1% NM. Four weeks later, the mice were sacrificed and their tumors were excised, weighed and processed for histological analysis. NM inhibited the growth of OHSU-974 tumors by 47% and tumor burden by 50%. At lower concentrations, NM demonstrated no effect on proliferation, but at 1,000 µg/ml a 40% toxicity was observed. Zymography revealed the MMP-2 and PMA-induced MMP-9 secretion. NM suppressed the secretion of both MMPs in a dose-dependent manner, with a virtual inhibition at 500 µg/ml. NM inhibited OHSU-974 cell invasion through Matrigel in a dose-dependent manner with a complete block at 1,000 µg/ml. H&E staining showed no morphological changes below 500 µg/ml. These results suggest that NM has potential therapeutic use in the treatment of human FA HNSCC.
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December 2012
Volume 41 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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  • Source Normalized Impact per Paper (SNIP): 0.88
  • SCImago Journal Rank (SJR): 1.099
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Spandidos Publications style
Roomi MW, Kalinovsky T, Roomi NW, Niedzwiecki A and Rath M: In vitro and in vivo inhibition of human Fanconi anemia-associated head and neck squamous cell carcinoma by a novel nutrient mixture. Int J Oncol 41: 1996-2004, 2012.
APA
Roomi, M.W., Kalinovsky, T., Roomi, N.W., Niedzwiecki, A., & Rath, M. (2012). In vitro and in vivo inhibition of human Fanconi anemia-associated head and neck squamous cell carcinoma by a novel nutrient mixture. International Journal of Oncology, 41, 1996-2004. https://doi.org/10.3892/ijo.2012.1639
MLA
Roomi, M. W., Kalinovsky, T., Roomi, N. W., Niedzwiecki, A., Rath, M."In vitro and in vivo inhibition of human Fanconi anemia-associated head and neck squamous cell carcinoma by a novel nutrient mixture". International Journal of Oncology 41.6 (2012): 1996-2004.
Chicago
Roomi, M. W., Kalinovsky, T., Roomi, N. W., Niedzwiecki, A., Rath, M."In vitro and in vivo inhibition of human Fanconi anemia-associated head and neck squamous cell carcinoma by a novel nutrient mixture". International Journal of Oncology 41, no. 6 (2012): 1996-2004. https://doi.org/10.3892/ijo.2012.1639