A Nutrient Mixture Inhibits MMP Secretion, Invasion, Growth, and Induction of Apoptosis in Human Tongue Cancer Cell Line SC-255

DOI: 10.4236/ojapo.2013.24006   PDF   HTML   XML   3,040 Downloads   7,878 Views  


A majority of oral cancers is squamous cell carcinoma and tongue carcinomas comprise 30% of all oral cancers. However, Phytochemicals, herbal and dietary antioxidants have been reported to prevent cancers. A nutrient mixture containing, ascorbic acid, lysine, proline and green tea extract, among other nutrients, has previously been shown to exhibit a broad spectrum chemo preventative and therapeutic anti-cancer properties in a number of cell lines. In a recent study, we found that the nutrient mixture significantly inhibited acetaminophen induced hepatic and renal toxicity, and it suppressed carbon tetrachloride induced hepatic toxicity in ICR mice as well. This study was undertaken to determine if the nutrient mixture is useful in inhibiting various parameters of cancer progression on human tongue cancer cell line SC-255. SC-255 cells were grown in a Dulbecco’s Eagle medium and treated with the nutrient mixture at 0, 10, 50, 100, 500 and 1000 μg/ml, in triplicate. The nutrient mixture exhibited 20% and 30% toxicity at 500 and 1000 μg/ml, respectively. Zymography demonstrated the expression of MMP-2 and MMP-9; and PMA treatment further enhanced MMP-9 activity. The nutrient mixture inhibited the secretion of MMP-2 and MMP-9 in a dose-dependent fashion with a total inhibition at 500 μg/ml. Matrigel invasion was significantly reduced by 40%, 80% and 100% at 100, 500 and 1000 μg/ml, respectively. The nutrient mixture also inhibited cell migration and induced apoptosis in a dose response fashion. Thus, the nutrient mixture may have a potential in the tongue cancer treatment.

Share and Cite:

M. Roomi, N. Roomi, B. Bhanap, A. Niedzwiecki and M. Rath, "A Nutrient Mixture Inhibits MMP Secretion, Invasion, Growth, and Induction of Apoptosis in Human Tongue Cancer Cell Line SC-255," Open Journal of Apoptosis, Vol. 2 No. 4, 2013, pp. 37-44. doi: 10.4236/ojapo.2013.24006.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] W. J. Blot, J. K. McLaughlin, D. M. Winn, D. F. Austin, R. S. Greenberg, S. Preston-Martin, L. Bernstein, et al. “Smoking and Drinking in Relation to Oral and Pharyngeal Cancer,” Cancer Research, Vol. 48, No. 11, 1988, pp. 3282-3287.
[2] S. Y. Choi and H. Kahyo, “Effect of Cigarette Smoking and Alcohol Consumption in the Aetiology of Cancer of the Oral Cavity, Pharynx and Larynx,” International Journal of Epidemiology, Vol. 20, No. 4, 1991, pp. 878-885. http://dx.doi.org/10.1093/ije/20.4.878
[3] A. Mashberg, P. Boffetta, R. Winkelman and L. Garfinkel, “Tobacco Smoking, Alcohol Drinking, and Cancer of the Oral Cavity and Oropharynx among US Veterans,” Cancer, Vol. 72, No. 4, 1993, pp. 1369-1375. http://dx.doi.org/10.1002/1097-0142(19930815)72:4<1369::AID-CNCR2820720436>3.0.CO;2-L
[4] C. B. Heffernan, J. P. O’Neill and C. Timon, “Oncogenic Impact of Human Papilloma Virus in Head and Neck Cancer,” Journal of Laryngology Otology, Vol. 124, No. 9, 2010, pp. 941-944. http://dx.doi.org/10.1017/S0022215110001179
[5] P. T. Hennessey, W. H. Westra and J. A. Califano, “Human Papillomavirus and Head and Neck Squamous Cell Carcinoma: Recent Evidence and Clinical Implications,” Journal of Dental Research, Vol. 88, No. 4, 2009, pp. 300-306. http://dx.doi.org/10.1177/0022034509333371
[6] M. Evans and N. G. Powell, “The Changing Aetiology of Head and Neck Cancer: The Role of Human Papillomavirus,” Clinical Oncology, Vol. 22, No. 7, 2010, pp. 538-546. http://dx.doi.org/10.1016/j.clon.2010.05.024
[7] C. R. Trivedy, G. Craig and S. Warnakulasuriya, “The Oral Health Consequences of Chewing Areca Nut,” Addiction Biology, Vol. 7, No. 1, 2002, pp. 115-125. http://dx.doi.org/10.1080/13556210120091482
[8] M. Bloching, M, W. Reich, J. Schubert, T. Grummt and A. Sandner, “Micronucleus Rate of Buccal Mucosal Epithelial Cells in Relation to Oral Hygiene and Dental Factors,” Oral Oncology, Vol. 44, No. 3, 2008, pp. 220-226. http://dx.doi.org/10.1016/j.oraloncology.2007.02.002
[9] N. Taghavi and I. Yazdi, “Type of Food and Risk of Oral Cancer,” Archives of Iranian Medicine, Vol. 10, No. 2, 2007, pp. 227-232. http://dx.doi.org/10.1093/annonc/mdg448
[10] C. Pelucchi, R. Talamini, E. Negri, F. Levi, E. Conti, S. Franceschi and C. La Vecchia, “Folate Intake and Risk of Oral and Pharyngeal Cancer,” Annals of Oncology, Vol. 14, No. 11, 2003, pp. 1677-1681.
[11] American Cancer Society, “Oral Cavity and Oropharyngeal Cancer,” 2013. http://www.cancer.org/acs/groups/cid/documents/webcontent/003128-pdf.pdf
[12] NIDCR, “Oral Cancer 5-Year Survival Rates by Race, Gender, and Stage of Diagnosis,” 2004.
[13] R. W. Dolan, C. W. Vaughan and N. Fuleihan, “Symptoms in Early Head and Neck Cancer: An Inadequate Indicator,” Otolaryngology Head Neck Surgery, Vol. 119, No. 5, 1998, pp. 463-467. http://dx.doi.org/10.1016/S0194-5998(98)70102-0
[14] M. D. Ellison and B. H. Campbell, “Screening for Cancer of the Head and Neck: Addressing the Problem,” Surgical Oncology Clinics of North America, Vol. 8, No. 4, 1999, pp. 725-734.
[15] R. P. Takes, A. Rinaldo, C. E. Silver, J. F. Piccirillo, M. Haigentz Jr., C. Suárez, et al., “Future of the TNM Classification and Staging System in Head and Neck Cancer,” Head & Neck, Vol. 32, No. 2, 2010, pp. 1693-1711. http://dx.doi.org/10.1002/hed.21361
[16] J. S. Greenberg, R. Fowler, J. Gomez, V. Mo, D. Roberts, A. K. El-Naggar, et al., “Extent of Extracapsular Spread: A Critical Prognosticator in Oral Tongue Cancer,” Cancer, Vol. 97, No. 6, 2003, pp. 1464-1470. http://dx.doi.org/10.1002/cncr.11202
[17] M. Rath and L. Pauling, “Plasmin-Induced Proteolysis and the Role of Apoprotein (a), Lysine and Synthetic Analogs,” Orthomolecular Medicine, Vol. 7, No. 1, 1992, pp. 17-23.
[18] M. W. Roomi, N. Roomi, V. Ivanov, T. Kalinovsky, A. Niedzwiecki and M. Rath, “Inhibition of Pulmonary Metastasis of Melanoma B16FO Cells in C57BL/6 Mice by a Nutrient Mixture Consisting of Ascorbic Acid, Lysine, Proline, Arginine, and Green Tea Extract,” Experimental Lung Research, Vol. 32, No. 10, 2006, pp. 517-30. http://dx.doi.org/10.1080/01902140601098552
[19] M. W. Roomi, T. Kalinovsky, N. W. Roomi, A. Niedzwiecki and M. Rath, “Inhibition of SK-N-MC Human Neuroblastoma Cell Line in Vivo and in Vitro by a Novel Nutrient Mixture,” Oncology Reports, Vol. 29, No. 5, 2013, pp. 1714-1720
[20] M. W. Roomi, V. Ivanov, S. Netke, T. Kalinovsky, A. Niedzwiecki and M. Rath, “In Vivo and in Vitro Antitumor Effect of Ascorbic Acid, Lysine, Proline and Green Tea Extract on Human Melanoma Cell Line A2058,” In Vivo, Vol. 20, No. 1, 2006, pp. 25-32.
[21] M. W. Roomi, N. Roomi, V. Ivanov, T. Kalinovsky, A. Niedzwiecki and M. Rath, “Inhibitory Effect of a Mixture Containing Ascorbic Acid, Lysine, Proline and Green Tea Extract on Critical Parameters in Angiogenesis,” Oncology Reports, Vol. 14, No. 4, 2005, pp. 807-815.
[22] D. Bourboulia and W. G. Stetler-Stevenson,“Matrix Metalloproteinases (MMPs) and Tissue Inhibitors of Metalloproteinases (TIMPs): Positive and Negative Regulators in Tumor Cell Adhesion,” Seminars in Cancer Biology, Vol. 20, No. 3, 2010, pp. 161-168. http://dx.doi.org/10.1016/j.semcancer.2010.05.002
[23] B. P. Patel, S. V. Shah, S. N. Shukla, P. M. Shah and P. S. Patel, “Clinical Significance of MMP-2 and MMP-9 in Patients with Oral Cancer,” Head Neck, Vol. 29, No. 6, 2007, pp. 564-572. http://dx.doi.org/10.1002/hed.20561
[24] H. Kawamata, D. Uchida, H. Hamano, T. Kimura-Yanagawa, K. I. Nakashiro, S. Hino, F. Omotehara, H. Yoshida and M. Sato, “Active-MMP2 in Cancer Cell Nests of Oral Cancer Patients: Correlation with Lymph Node Metastasis,” International Journal of Oncology, Vol. 13, No. 4, 1998, pp. 699-704.
[25] M. Sutinen, T. Kainulainen, T. Hurskainen, E. Vesterlund, J. P. Alexander, C. M. Overall, et al., “Expression of Matrix Metalloproteinases (MMP-1 and -2) and Their Inhibitors (TIMP-1, -2 and -3) in Oral Lichen Planus, Dysplasia, Squamous Cell Carcinoma and Lymph Node Metastasis,” British Journal of Cancer, Vol. 77, No. 12, 1998, pp. 2239-2245. http://dx.doi.org/10.1038/bjc.1998.372
[26] S. Kurahara, M. Shinohara, T. Ikebe, S. Nakamura, M. Beppu, A. Hiraki, et al., “Expression of MMPS, MT-MMP, and TIMPs in Squamous Cell Carcinoma of the Oral Cavity: Correlations with Tumor Invasion and Metastasis,” Head Neck, Vol. 21, No. 7, 1999, pp. 627-638. http://dx.doi.org/10.1002/(SICI)1097-0347(199910)21:7<627::AID-HED7>3.0.CO;2-2
[27] Z. L. Gokaslan, S. K. Chintala, J. E. York, V. Boyapati, S. Jasti, R. Sawaya, et al., “Expression and Role of Matrix Metalloproteinases MMP-2 and MMP-9 in Human Spinal Column Tumors,” Clinical and Experimental Metastasis, Vol. 16, No. 8, 1998, pp. 721-728. http://dx.doi.org/10.1023/A:1006580728338
[28] M. W. Roomi, V. Ivanov, S. P. Netke, A. Niedzwiecki, M. Rath, “Serum Markers of the Liver, Heart, and Kidney and Lipid Profile and Histopathology in ODS Rats Treated with Nutrient Synergy,” Journal of the American College of Nutrition, Vol. 22, No. 5, 2003, p. 477.
[29] M. W. Roomi, T. Kalinovsky, N. W. Roomi, V. Ivanov, M. Rath, A. Niedzwiecki, “A Nutrient Mixture Suppresses Carbon Tetrachloride-Induced Acute Hepatic Toxicity in ICR Mice,” Human and Experimental Toxicology, Vol. 22, No. 7, 2008, pp. 559-566. http://dx.doi.org/10.1177/0960327108096851
[30] M. W. Roomi, T. Kalinovsky, V. Ivanov, M. Rath, A. A. Niedzwiecki, “A Nutrient Mixture Prevents Acetaminophen Hepatic and Renal Toxicity in ICR Mice,” Human and Experimental Toxicology, Vol. 27, No. 3, 2008, pp. 223-230. http://dx.doi.org/10.1177/0960327108090276
[31] M. W. Roomi, N. W. Roomi, M. Rath and A. Niedzwiecki, “Prevention of Adriamycin Hepatic and Renal Toxicity in Male BALB/c Mice by a Nutrient Mixture,” Presented at the 50th Annual Meeting of Society of Toxicology, March 2011, p. 476.
[32] M. W. Roomi, N. W. Roomi, M. Rath and A. Niedzwiecki, “Prevention of Amiodarone-Induced Pulmonary and Cardiac Toxicity in Male BALB/c Mice by a Nutrient Mixture,” Presented at the 51st Annual Meeting of Society of Toxicology, San Francisco, 11-15 March 2012, Abstract #2413.

comments powered by Disqus

Copyright © 2020 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.