GLUT1 Bioactive Triterpenoids from <i>Commiphora mukul</i> Suppresses Glycolysis and Induces Apoptosis in Breast Cancer Cells

Cancer cells rely heavily on glycolysis for energy production and survival. Therefore, targeting glycolysis represents a promising therapeutic approach to cancer treatment. This study investigates the anticancer potential of myrrhanone B (MN) and myrrhanol B (ML), two bioactive triterpenoids isolated from the ethyl acetate extract of <i>Commiphora mukul</i> (CMEE), with a particular focus on their effects on cancer metabolism and apoptosis. The cytotoxic effects of CMEE, MN, and ML were evaluated in MCF-7 and MDA-MB-231 breast cancer cell lines by using MTT assays. Molecular docking and molecular dynamics (MD) simulations were performed to examine interactions with glucose transporter-1 (GLUT1). Glucose uptake and lactate production were assessed calorimetrically to determine their impact on glycolysis. Apoptosis was analyzed using flow cytometry with annexin V/PI staining, while reactive oxygen species (ROS) levels and caspase-3 activity were measured to explore oxidative stress and apoptotic pathways. CMEE, MN, and ML significantly reduced cell viability in a dose-dependent manner, with IC₅₀ values at 48 h of 30 μg/mL for CMEE, 18 μM for MN, and 23 μM for ML in MDA-MB-231 cells and 40 μg/mL for CMEE, 22 μM for MN, and 27 μM for ML in MCF-7 cells. <i>In vitro</i>, glucose uptake and lactate levels were significantly reduced in MDA-MB-231 and MCF-7 cells following treatment with IC₅₀ concentrations of MN, ML, and CMEE, suggesting a strong antiglycolytic effect. <i>In silico</i> docking and simulation predict good complementarity of MN and ML with GLUT1 protein and high binding affinity for the GLUT1 receptor, which may be a probable drug target for these compounds. Furthermore, apoptosis assays revealed a significant increase in early and late apoptotic cell populations following treatment with IC₅₀ doses of CMEE, MN, and ML, which correlate with the elevated intracellular ROS levels and enhanced caspase-3 activity. CMEE and its bioactive compounds, MN and ML, exert potent anticancer effects by glycolysis suppression, elevating ROS levels, and promoting apoptosis in MDA-MB-231 and MCF-7 breast cancer cells.