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GLUT1 Bioactive Triterpenoids from Commiphora mukul Suppresses Glycolysis and Induces Apoptosis in Breast Cancer Cells

Year: 2025

Type: article

Abstract: High Resolution Image Download MS PowerPoint Slide 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 Commiphora mukul (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 IC 50 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. In vitro, glucose uptake and lactate levels were significantly reduced in MDA-MB-231 and MCF-7 cells following treatment with IC 50 concentrations of MN, ML, and CMEE, suggesting a strong antiglycolytic effect. In silico 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 IC 50 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.

Source: ACS Omega

DOI: 10.1021/acsomega.5c03147