Immunological Profiles of Cancer Bearing Mice Fed a Black Raspberry Mediated Diet
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Date
2021-05
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The Ohio State University
Abstract
Cancers of the pharynx and oral cavity account for 3% of new cancer cases in the United States each year. Approximately 90% of these cancers manifest as Head and Neck Squamous Cell Carcinoma. Recent preclinical trials have demonstrated the ability of black raspberries (BRBs) to inhibit oral carcinogenesis; however, the mechanisms behind this chemoprevention are not fully understood. Using the 4-nitroquinoline n-oxide (4NQO) carcinogen model of oral carcinogenesis, we induced head and neck cancers in wild type C57BL/6 mice. These mice were then fed either AIN-76A control diet or control diets supplemented with BRB, BRB-extract (BRB-E), protocatechuic acid (PCA, a constituent of BRB), or ellagic acid (EA, a BRB phytochemical). Mice were exposed to water containing 100 µg/mL 4NQO carcinogen for 16 weeks, after which they were exposed to clean drinking water for 8 weeks. Mice were then sacrificed, tumors and lesions of the tongue were counted, and the spleens and draining lymph nodes were collected. We isolated and plated single cell suspensions from spleens and lymph nodes of these mice, in the presence or absence of anti-CD3 antibodies and soluble CD28 antibodies. Sandwich cytokine enzyme-linked immunosorbent assays (ELISAs) were then performed on cell culture supernatants of these samples for the cytokines IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α, and IFNγ. Dietary supplementation with BRB showed a significant decrease in IL-17 in the draining lymph nodes, as well as a significant increase in IL-2 in the spleen. These differences were also associated with a significant decrease in lesion multiplicity of mice fed the BRB supplemented diet. Our results demonstrate that, in the mouse 4NQO oral cancer model, the administration of dietary BRB inhibits oral carcinogenesis by mediating T-cell activation, proliferation, and differentiation. This provides an intriguing basis for follow up studies to further explore BRBs role in immune system regulation and oral carcinogenesis.
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Keywords
Cancer, Black Raspberry, ELISA, Cytokine, Oral cancer, T cell