Suppression of the Tumorigenic Phenotype in Human Oral Squamous Cell Carcinoma Cells by an Ethanol Extract Derived From Freeze-Dried Black Raspberries

Kapila Rodrigo

Yeshwant Rawal

Robert Renner

Steven Schwartz

Qingguo Tian

Peter Larsen

Susan Mallery

K. A. Rodrigo, R. J. Renner, P. E. Larsen, and S. R. Mallery are affiliated with the Department of Oral Maxillofacial Surgery and Pathology, College of Dentistry, The Ohio State University, Columbus, Ohio 43210. Y. Rawal is affiliated with the Department of Biologic and Diagnostic Sciences, University of Tennessee Health Science Center, Memphis, TN 40536. S. J. Schwartz and Q. Tian are affiliated with the Department of Food Science, College of Agriculture, The Ohio State University, Columbus, Ohio 43210.

Address correspondence to Susan R. Mallery, Department of Oral Maxillofacial Surgery and Pathology, 305 West 12th Avenue, P.O. Box 182357, Columbus, OH 43218–2357. Phone: 614–292–5892. FAX: 614–292–9384. E-mail: ude.uso@1.yrellam

Abstract

Despite focused efforts to improve therapy, 5-yr survival rates for persons with advanced-stage oral squamous cell carcinoma (SCC) remain discouragingly low. Clearly, early detection combined with strategies for local intervention, such as chemoprevention prior to SCC development, could dramatically improve clinical outcomes. Previously conducted oral cavity human chemoprevention trials, however, have provided mixed results. Although some therapies showed efficacy, they were often accompanied by either significant toxicities or circulating antiadenoviral antibodies. It is clearly apparent that identification of nontoxic, effective treatments is essential to prevent malignant transformation of oral epithelial dysplasias. This study employed cell lines isolated from human oral SCC tumors to investigate the effects of a freeze-dried black raspberry ethanol extract (RO-ET) on cellular growth characteristics often associated with a transformed phenotype such as sustained proliferation, induction of angiogenesis, and production of high levels of reactive species. Our results demonstrate that RO-ET suppresses cell proliferation without perturbing viability, inhibits translation of the complete angiogenic cytokine vascular endothelial growth factor, suppresses nitric oxide synthase activity, and induces both apoptosis and terminal differentiation. These data imply that RO-ET is a promising candidate for use as a chemopreventive agent in persons with oral epithelial dysplasia.

Abstract

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