Plasma Cytokines as Potential Response Indicators to Dietary Freeze-Dried Black Raspberries in Colorectal Cancer Patients

Abstract

Oral consumption of freeze-dried black raspberries attenuated neoplastic changes in colorectal tissue markers of apoptosis, cell proliferation, and angiogenesis in colorectal cancer (CRC) patients. To determine whether plasma concentrations of interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-10, IL-12p70, granulocyte macrophage colony stimulating factor (GM-CSF), interferon-γ, and tumor necrosis factor-α (TNF-α) were associated with berry treatment and changes in colorectal tissue markers of apoptosis, cell proliferation, and angiogenesis, plasma and biopsy samples of adenocarcinoma and adjacent normal-appearing colorectal tissue were collected before and during berry treatment from 24 CRC patients who had not received prior therapy and drank a slurry of black raspberry powder (20 g in 100 ml drinking water) 3 times a day for 1 to 9 wk. Plasma concentrations of GM-CSF (+0.12 ± 0.04 pg/mL; P = 0.01) and IL-8 (-1.61 ± 0.71 pg/mL; P = 0.04) changed in patients receiving berries for more than 10 days. These changes were correlated with beneficial changes in markers of proliferation (r_{ΔGM-CSF, ΔKi67 carcinoma - normal} = −0.51) and apoptosis (r_{ΔIL-8, ΔTUNEL carcinoma - normal} = −0.52) observed in colorectal tissue taken within the same week. Plasma concentrations of GM-CSF and IL-8 may serve as noninvasive indicators to monitor tissue response to berry-based interventions for CRC.

ACKNOWLEDGMENTS

We thank the participants and managers of the CRC trial for their outstanding contribution to this project. Special thanks to Helen Rager and Yanyu Wang from the Clinical Support laboratory of SAIC Frederick, Inc. (Frederick, MD) for cytokine analysis of the plasma samples and Dr. Wendy Frankel (The Ohio State University, Columbus, OH) for histopathological analysis of tissue biopsies.

This study was funded by U.S. Department of Agriculture Grant 38903-03560, National Cancer Institute Grants CA103180 and CA148818, and the Intramural Research Program, National Cancer Institute, National Institutes of Health, Bethesda, MD.

Roycelynn A. Mentor-Marcel and Gerd Bobe contributed equally to the study.