Ali Ehab M M, Sonbul Sultan N, Almuhaini Eman A, Al-Ghafari Ayat B
Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
Department of Chemistry, Division of Biochemistry, Faculty of Science, Tanta University, Tanta, Egypt.
Int J Health Sci (Qassim). 2025 Mar-Apr;19(2):26-41.
This study aims to evaluate the synergistic effects of doxorubicin (DOX) and the natural phenolic alkaloid avenanthramide C (AVC) on enhancing apoptosis in MCF-7 breast cancer (BC) cells, with a specific focus on the expression of mitochondrial proteins voltage-dependent anion channel 2 (VDAC2) and mitochondrial carrier homolog 1 (MTCH1) involved in apoptosis pathways.
MCF-7 cells were treated with various concentrations of DOX and AVC. The 50% inhibitory concentration (IC) of DOX combined with AVC was evaluated in the MCF-7 cells using an MTT assay, while gene expression levels of , , and were assessed through real-time polymerase chain reaction. Apoptotic rates were measured using flow cytometry.
DOX and AVC combination reduced the IC value by 2.1-fold compared to DOX alone, indicating enhanced cytotoxicity. Co-treatment significantly downregulated expression and increased apoptosis by 76% in cells treated with 3 μM DOX and 160 μM AVC. Gene expression analysis revealed a 4.8-fold increase in MTCH1 and a 15-fold increase in VDAC2 compared to DOX treatment alone.
The DOX-AVC combination demonstrated a potent synergistic effect, enhancing apoptosis in BC cells by modulating mitochondrial pathways. This approach may provide a promising strategy for reducing chemotherapy side effects in BC treatment. Further studies in pre-clinical models are warranted to explore its therapeutic potential.
本研究旨在评估阿霉素（DOX）与天然酚类生物碱燕麦酰胺C（AVC）对增强MCF-7乳腺癌（BC）细胞凋亡的协同作用，特别关注参与凋亡途径的线粒体蛋白电压依赖性阴离子通道2（VDAC2）和线粒体载体同源物1（MTCH1）的表达。
用不同浓度的DOX和AVC处理MCF-7细胞。使用MTT法评估DOX与AVC联合在MCF-7细胞中的50%抑制浓度（IC），同时通过实时聚合酶链反应评估、和的基因表达水平。使用流式细胞术测量凋亡率。
与单独使用DOX相比，DOX和AVC联合使IC值降低了2.1倍，表明细胞毒性增强。在用3μM DOX和160μM AVC处理的细胞中，联合处理显著下调表达并使凋亡增加76%。基因表达分析显示，与单独使用DOX处理相比，MTCH1增加了4.8倍，VDAC2增加了15倍。
DOX-AVC联合显示出强大的协同作用，通过调节线粒体途径增强BC细胞的凋亡。这种方法可能为减少BC治疗中的化疗副作用提供一种有前景的策略。有必要在临床前模型中进行进一步研究以探索其治疗潜力。
