D-Mannose Upregulates Testin via the NF-κB Pathway to Inhibit Breast Cancer Proliferation

d-Mannose is a naturally occurring monosaccharide known to enhance the effects of chemotherapy, immunotherapy, and radiotherapy in cancer patients. This study aimed to investigate the growth-regulating mechanism of d-mannose on breast cancer (BC) cells. d-mannose was treated on MDA-MB-231 and MCF-7 BC cells. Cell counting kit-8 (CCK-8), wound healing test, transwell invasion, and flow cytometry assays were used to assess the viability, invasion, migration, and apoptosis of d-mannose treated BC cells. Testin (TES) expressions in d-mannose treated BC cells were evaluated using western blot analysis, qRT-PCR, and immunofluorescence assays. The potential regulatory relationship between d-mannose and TES in BC cells were explored by analyzing TES gene expression profile in BC cells using the University of California Santa Cruz (UCSC) Xena browser database. Immunohistochemical analysis of TES protein was performed in BC tissue samples obtained from patients. It was found that d-mannose significantly inhibited the growth of MDA-MB-231 and MCF-7 cells in a concentration and time-dependent manner by activating the NF-κB signaling pathway and upregulating TES expression. TES knockdown downregulated the NF-κB1, NF-κB2, and p65 protein expressions. Therefore, this study highlights that d-mannose have the potential to promote anticancer effects upon further trials using in vivo models and clinical studies.