Dietary Consumption of Black Raspberries or Their Anthocyanin Constituents Alters Innate Immune Cell Trafficking in Esophageal Cancer

Abstract

Freeze-dried black raspberries (BRB), their component anthocyanins (AC), and a metabolite of BRB ACs, protocatechuic acid (PCA), inhibit the development of esophageal cancer in rats induced by the carcinogen, N-nitrosomethylbenzylamine (NMBA). All three components reduce inflammation in the esophagus and in plasma. The present study determined the relation of changes in inflammatory markers to infiltration of innate immune cells into NMBA-treated esophagus. Rats were injected with NMBA (0.35 mg/kg) for 5 weeks while on control diet. Following NMBA treatment, rats were fed diets containing 6.1% BRB powder, an AC-rich fraction of BRBs (3.8 mmol/g), or 500 ppm PCA. At weeks 15, 25, and 35, inflammatory biomarker expression in the plasma and esophagus was quantified, and infiltration of immune cells in the esophagus was examined. At all three time points, BRB, AC, and PCA similarly affected cytokine production in the esophagus and plasma of NMBA-treated rats, relative to the NMBA-only control. These included decreased expression of the proinflammatory cytokine IL1b and increased expression of the anti-inflammatory cytokine IL10. Moreover, all three diets also increased the expression of IL12, a cytokine that activates both cytolytic natural killer and CD8 þ T cells. In addition, the three diets also decreased infiltration of both macrophages and neutrophils into the esophagus. Overall, our results suggest that another mechanism by which BRBs, ACs, and PCA inhibit NMBA-induced esophageal tumorigenesis is by altering cytokine expression and innate immune cell trafficking into tumor tissues.

Black Raspberries and Their Anthocyanin and Fiber Fractions Alter the Composition and Diversity of Gut Microbiota in F-344 Rats

“…Our current study observed significantly increased abundance of Akkermansia by BRB diet and increased abundance of Desulfovibrio by the BRB residue fraction in rats. Previously, we demonstrated that whole BRBs, anthocyanins and the residue fraction decreased cellular proliferation marker Ki67 and inflammatory biomarkers, including cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), nuclear factor (NF)-κB, soluble epoxide hydrolase (sEH), pentraxin-3 (PTX3), and prostaglandin E 2 (PGE 2 ), in the NMBA-induced esophageal cancer in rats (11, 43, 44), suggesting that all three diets can suppress tumorigenesis by inhibiting inflammation. In the current study, rats fed whole BRBs or the residue fraction had increased abundance of Akkermansia and Desulfovibrio suggesting that they might contribute to the anti-inflammatory effects of whole BRBs and the residue fraction.…”

Inhibition of the development of N-nitrosomethylbenzylamine-induced esophageal tumors in rats by strawberries and aspirin, alone and in combination

“…Our laboratory focuses on chemoprevention of colorectal cancer [47–57] and ESCC [30–41], using different types of berries. Strawberries have been protective against a number of cancers, including prostate cancer, cervical cancer, ovarian cancer, hepatoma, leukemia, and melanoma [29].…”

“…One focus of our laboratory is the chemopreventive effects of berries against ESCC [30–41]. Carlton, et al previously demonstrated that both 5% and 10% strawberries reduced the multiplicity of rat esophageal tumors induced by the carcinogen N -nitrosomethylbenzylamine (NMBA) [42].…”

An immunological perspective for preventing cancer with berries

“…Our group investigated the ability of BRBs, BRB components (such as AC), and BRB metabolites (such as PCA) to inhibit N-nitrosomethylbenzylamine (NMBA)-induced esophageal cancer and to modulate immune cell trafficking in rats [40]. All rats were injected with NMBA and then they were fed with either a control AIN-76A diet, or the control diet supplemented with either 6.1% of BRB powder (freeze-dried whole BRBs), an AC-rich fraction of BRBs (3.8 μmol/g), or PCA (500 ppm) for 35 weeks.…”