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Bioactive compounds or metabolites from black raspberries modulate T lymphocyte proliferation, myeloid cell
Thomas A Mace1, Samantha A King, Zeenath Ameen
1Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, 302B Comprehensive Cancer Center, 400 W. 12th Ave., Columbus, OH, 43210, USA.
Abstract:
Bioactive phytochemicals from natural products, such as black raspberries (BRB; Rubus occidentalis), have direct anticancer properties on malignant cells in culture and in xenograft models. BRB components inhibit cancer progression in more complex rodent carcinogenesis models. Although mechanistic targets for BRB phytochemicals in cancer cells are beginning to emerge, the potential role in modulating host immune processes impacting cancer have not been systematically examined. We hypothesized that BRB contain compounds capable of eliciting potent immunomodulatory properties that impact cellular mediators relevant to chronic inflammation and tumor progression. We studied both an ethanol extract from black raspberries (BRB-E) containing a diverse mixture of phytochemicals and two abundant phytochemical metabolites of BRB produced upon ingestion (Cyanidin-3-Rutinoside, C3R; Quercitin-3-Rutinoside, Q3R). BRB-E inhibited proliferation, and viability of CD3/CD28 activated human CD4(+) and CD8(+) T lymphocytes. BRB-E also limited in vitro expansion of myeloid-derived suppressor cells (MDSC) and their suppressive capacity. Pre-treatment of immune cells with BRB-E attenuated IL-6-mediated phosphorylation of signal transducer and activator of transcription-3 (STAT3) and IL-2-induced STAT5 phosphorylation. In contrast, pre-treatment of immune cells with the C3R and Q3R metabolites inhibited MDSC expansion, IL-6-mediated STAT3 signaling, but not IL-2-induced STAT5 phosphorylation and were less potent inhibitors of T cell viability. Together these data indicate that BRB extracts and their physiologically relevant metabolites contain phytochemicals that affect immune processes relevant to carcinogenesis and immunotherapy. Furthermore, specific BRB components and their metabolites may be a source of lead compounds for drug development that exhibits targeted immunological outcomes or inhibition of specific STAT-regulated signaling pathways.
Insights
Black raspberries (BRB) and their metabolites impact immune cells, potentially inhibiting cancer progression. These natural compounds affect T cells and myeloid-derived suppressor cells, offering leads for cancer drug development.
Area of Science:
- Natural product chemistry
- Immunology
- Cancer research
Background:
- Black raspberries (BRB) possess anticancer properties, but their immune-modulating effects are underexplored.
- Understanding BRB's impact on immune cells is crucial for cancer prevention and therapy.
Purpose of the Study:
- To investigate the immunomodulatory effects of black raspberry extract (BRB-E) and its metabolites on immune cells.
- To determine the impact of BRB components on T cell proliferation, myeloid-derived suppressor cells (MDSC), and STAT signaling pathways relevant to cancer.
Main Methods:
- Treatment of human CD4(+) and CD8(+) T lymphocytes and MDSCs with BRB-E, Cyanidin-3-Rutinoside (C3R), and Quercitin-3-Rutinoside (Q3R).
- Assessed T cell proliferation and viability, MDSC expansion and suppressive function.
- Analyzed STAT3 and STAT5 phosphorylation via Western blotting after IL-6 and IL-2 stimulation.
Main Results:
- BRB-E inhibited T cell proliferation and viability, and limited MDSC expansion and suppressive capacity.
- BRB-E and its metabolites (C3R, Q3R) attenuated IL-6-mediated STAT3 signaling.
- C3R and Q3R were less potent inhibitors of T cell viability and did not affect IL-2-induced STAT5 phosphorylation compared to BRB-E.
Conclusions:
- Black raspberry extracts and their metabolites modulate immune cell functions relevant to cancer.
- BRB phytochemicals impact T cells and MDSCs, suggesting potential for cancer immunotherapy and drug development.
- Specific BRB components may serve as leads for developing targeted therapies affecting immune responses and STAT signaling.
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