Anticancer Effects of the Polysaccharide Fraction of Bioprocessed Black Rice Bran Extract in Triple-Negative Breast Cancer (TNBC) Cells and Radiotherapy-Resistant TNBC Cells by Inhibiting Interactions with Endothelial Cells and Inducing Natural Killer Cell Activity

Abstract

The tumor microenvironment, comprising elements such as endothelial cells (ECs) and immune cells, plays a critical role in cancer progression, therapy resistance, and metastasis. Adhesion of cancer cells to the endothelium, their transendothelial migration, and immune evasion by cancer cells contribute to these processes. In this study, we investigated the effect of the polysaccharide-rich fraction derived from bioprocessed black rice bran extract (BRB-F-P) on the interaction between triple-negative breast cancer (TNBC) and radiotherapy-resistant TNBC (RT-R-TNBC) cells with ECs, as well as on the cytolytic function of natural killer (NK) cells. BRB-F-P treatment did not affect the viability of ECs, TNBC, or RT-R-TNBC cells. However, BRB-F-P (50 and 100 mu g/mL) significantly suppressed the clonogenicity of TNBC and RT-R-TNBC cells and attenuated ATP-induced expression of vascular adhesion molecule-1, intercellular adhesion molecule-1, and Vimentin, along with the phosphorylation of vascular endothelial cadherin in ECs. Additionally, BRB-F-P markedly reduced cancer cell adhesion to ECs and inhibited their ability to transmigrate through ECs. Interestingly, BRB-F-P increased NK cell-mediated cytotoxicity against TNBC and RT-R-TNBC cells by inducing granzyme B release and downregulating human leukocyte antigen-E expression in target cancer cells. These results suggest that BRB-F-P exerts anticancer effects in TNBC and RT-R-TNBC by inhibiting interactions with ECs and inducing NK cell activity without cytotoxicity.