Zeb Ahmad, Bolivar Avila Santiago Jr, Saleem Adeel, Rahman Shaikh Mizanoor, Ullah Kifayat, Ur Rahman Hayat, Halim Sobia Ahsan, Khan Shab Niaz, Sikandar Numan, Ullah Anwar, Al-Harrasi Ahmed, Ur Rehman Najeeb
Department of Biosciences, COMSATS University Islamabad, Park Road, Tarlai Kalan, Islamabad 45550, Pakistan.
Institute of Chemistry Rosario (IQUIR, CONICET-UNR) and Faculty of Biochemical and Pharmaceutical Sciences, National University of Rosario, Suipacha 531, Rosario, Santa Fe S2002LRK, Argentina.
ACS Omega. 2025 Sep 9;10(37):42369-42380. doi: 10.1021/acsomega.5c03147. eCollection 2025 Sep 23.
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 (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 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. , glucose uptake and lactate levels were significantly reduced in MDA-MB-231 and MCF-7 cells following treatment with IC concentrations of MN, ML, and CMEE, suggesting a strong antiglycolytic effect. 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 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.
癌细胞严重依赖糖酵解来产生能量和维持生存。因此，靶向糖酵解是一种很有前景的癌症治疗方法。本研究调查了没药酮B（MN）和没药醇B（ML）的抗癌潜力，这两种生物活性三萜类化合物是从（CMEE）的乙酸乙酯提取物中分离得到的，特别关注它们对癌症代谢和凋亡的影响。通过MTT法评估CMEE、MN和ML对MCF - 7和MDA - MB - 231乳腺癌细胞系的细胞毒性作用。进行分子对接和分子动力学（MD）模拟以检查与葡萄糖转运蛋白-1（GLUT1）的相互作用。通过量热法评估葡萄糖摄取和乳酸产生，以确定它们对糖酵解的影响。使用膜联蛋白V/PI染色的流式细胞术分析凋亡，同时测量活性氧（ROS）水平和半胱天冬酶-3活性以探索氧化应激和凋亡途径。CMEE、MN和ML以剂量依赖性方式显著降低细胞活力，在MDA - MB - 231细胞中，48小时时CMEE的IC值为30μg/mL，MN为18μM，ML为23μM；在MCF - 7细胞中，CMEE为40μg/mL，MN为22μM，ML为27μM。此外，用MN、ML和CMEE的IC浓度处理后，MDA - MB - 231和MCF - 7细胞中的葡萄糖摄取和乳酸水平显著降低，表明具有强烈的抗糖酵解作用。分子对接和模拟预测MN和ML与GLUT1蛋白具有良好的互补性，对GLUT1受体具有高结合亲和力，这可能是这些化合物的一个潜在药物靶点。此外，凋亡分析显示，用CMEE、MN和ML的IC剂量处理后，早期和晚期凋亡细胞群体显著增加，这与细胞内ROS水平升高和半胱天冬酶-3活性增强相关。CMEE及其生物活性化合物MN和ML通过抑制糖酵解、升高ROS水平以及促进MDA - MB - 231和MCF - 7乳腺癌细胞凋亡发挥强大的抗癌作用。
