High Glucose-reduced Apoptosis in Human Breast Cancer Cells Is Mediated by Activation of NF-κB

Tumor cells rely on glycolysis for their energy supply with the production of lactate even in normoxia condition, which is named aerobic glycolysis or Warburg effect. Therefore, high glucose (HG) concentration provides a favorable condition for increasing proliferation, angiogenesis and decreasing apoptosis, but its molecular mechanisms are still unknown. The objective of this study is to investigate HG condition on tumor cells behavior including proliferation, apoptosis, and an angiogenesis mediator. In this study, MCF-7 derived from human breast adenocarcinoma, were cultured in DMEM with two different concentrations of glucose for 48 h (5.5 mM as normal glucose (NG) condition and 25 mM as HG condition). We used Zingiber officinale extraction for the inhibition of NF-κB. Cell proliferation assay was done by direct counting, cell viability by MTT method, bcl-2 by Immunocytochemistry, apoptosis by Hoechst/PI double staining and vascular endothelium growth factor (VEGF) by ELISA. Results showed that HG increased lactate production, significantly. HG increased cell proliferation, cell viability, VEGF secretion, and bcl-2 expression while it decreased apoptosis. However, when HG was combined with Zingiber officinale extraction, cell proliferation, cell viability, VEGF secretion and bcl-2 expression decreased and apoptosis increased significantly due to inhibition of NF-κB. Results revealed that HG increased cell proliferation, angiogenesis and decreased apoptosis due to activation of NF-κB pathway. Moreover, the probable mechanism of the activation of NF-κB in HG is increasing reactive oxygen species (ROS) in this condition that can activate NF-κB directly.