Bioprocessed black rice bran potentiates the growth inhibitory activity of an immune checkpoint inhibitor against murine colon carcinoma

Authors: LEE, KYUNG HEE - Str Biotech Co Ltd; KWON, KI SUN - Str Biotech Co Ltd; HWANG, WOON SANG - Str Biotech Co Ltd; LEE, WHA YOUNG - Str Biotech Co Ltd; KIM, JEANMAN - Str Biotech Co Ltd; LEE, SANG JONG - Str Biotech Co Ltd; KIM, SUNG PHIL - Str Biotech Co Ltd; Friedman, Mendel

Submitted to: Food and Nutrition Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/10/2023
Publication Date: 12/13/2023
Citation: Lee, K., Kwon, K., Hwang, W., Lee, W., Kim, J., Lee, S., Kim, S., Friedman, M. 2023. Bioprocessed black rice bran potentiates the growth inhibitory activity of an immune checkpoint inhibitor against murine colon carcinoma. Food and Nutrition Sciences. 14:1149-1171. https://doi.org/10.4236/fns.2023.1412072.
DOI: https://doi.org/10.4236/fns.2023.1412072

Interpretive Summary: Black rice bran, a waste product produced during the milling process of black rice which removes the bran and germ and leaves the starchy endosperm, contains bioactive phenolic, flavonoid, and phytosteroid compounds that may be responsible for reported antioxidant and anti-inflammatory activities resulting in health-promoting effects including antiproliferative properties. The bioprocessed black rice bran used in this study is a fermentation product of black rice bran using shiitake mushroom mycelia. Immune checkpoint inhibitors that affect antitumor immune cells are used in medicine for the treatment of a wide range of cancers. To our knowledge, immune checkpoint inhibitors have not previously been evaluated in combination with anticancer functional foods. The described results show that administering the new food product to mice with colon tumors significantly reduced tumor size by approximately 48%, as compared to the control diet. The additional administration of an immune checkpoint inhibitor potentiated (increased) the reduction in tumor size from about 48% to 63%, which was significant. The mechanism that governs the anti-tumor effects is like that reported for medical human chemotherapies. There is, therefore, a need for future clinical studies to investigate if dietary bioprocessed black rice bran supplemented to widely consumed foods such as breads, flatbreads, corn-based tortillas, soy-based tofu, white rice as well animal feeds can help ameliorate and/or prevent human carcinomas.

Technical Abstract: This study determined the effect of orally fed polysaccharide-rich bioprocessed (fermented) black rice bran produced by culturing with shiitake (Lentinus edodes) mushroom mycelium on CT-26 colon cancer cells in vivo in an intracutaneously transplanted mouse tumor alone and in combination with intraperitoneally administered anti-PD-1 immune checkpoint inhibitor. Analysis of the isolated tumor weights at the end of the study shows that the average tumor size in control mice is 3.78 grams, and the average tumor size in mice treated with anti-PD-1 antibody is 2.16 grams. The average tumor size in mice treated with BRB-F alone is 2.25 grams, and the average tumor size in mice treated with anti-PD-1 antibody BRB-F combination is 1.38 grams. Thus, BRB-F or anti-PD-1 antibody alone each reduce tumor size by 40.5% or 42.9%, whereas the combination of BRB-F and anti-PD-1 antibody reduces tumor size by 63.5%, with their cooperative effect being statistically significant. The observed anti-tumor effects were accompanied by a series of biomarkers associated with cancer formation and inhibition. These results indicate that the reported potentiation of cancer therapy using drug-based medical chemotherapies with added checkpoint inhibitors in human patients are mechanistically similar with the functional food evaluated in the present study. These beneficial effects in mice challenge clinicians to investigate if the black rice bran food product can also protect against human cancer.