OBHS Drives Abnormal Glycometabolis Reprogramming via GLUT1 in Breast Cancer

Abstract

Due to the poor metabolic conditions fomenting the emergence of the Warburg effect (WE) phenotype, abnormal glycometabolism has become a unique and fundamental research topic in the field of tumor biology. Moreover, hyperglycemia and hyperinsulinism are associated with poor outcomes in patients with breast cancer. However, there are a few studies on anticancer drugs targeting glycometabolism in breast cancer. We hypothesized that Oxabicycloheptene sulfonate (OBHS), a class of compounds that function as selective estrogen receptor modulators, may hold potential in a therapy for breast cancer glycometabolism. Here, we evaluated concentrations of glucose, glucose transporters, lactate, 40 metabolic intermediates, and glycolytic enzymes using an enzyme-linked immunosorbent assay, Western blotting, and targeted metabolomic analysis in, in vitro and in vivo breast cancer models. OBHS significantly inhibited the expression of glucose transporter 1 (GLUT1) via PI3K/Akt signaling pathway to suppress breast cancer progression and proliferation. Following an investigation of the modulatory effect of OBHS on breast cancer cells, we found that OBHS suppressed the glucose phosphorylation and oxidative phosphorylation of glycolytic enzymes, leading to the decreased biological synthesis of ATP. This study was novel in highlighting the role of OBHS in the remodeling of tumor glycometabolism in breast cancer, and this is worth further investigation of breast cancer in clinical trials.