Faiyaz Syed Shah Mohammed, Ahmad Afza, Fatima Daniya, Shahid Syed Monowar Alam, Kaushik Gaurav, Verma Chaitenya, Tiwari Rohit Kumar, Kumar Vinay
Department of Physiology, College of Medicine, University of Ha'il, Ha'il, 81451, Saudi Arabia.
Department of Physiology, Radha Devi Jageshwari Memorial Medical College & Hospital, Muzzafarpur, Bihar- 844127, India.
J Inflamm Res. 2025 Jul 1;18:8657-8673. doi: 10.2147/JIR.S521756. eCollection 2025.
Lung carcinoma is a major contributor to cancer incidence and mortality worldwide. Chronic activation of NF-κB triggers activation of its target genes involved in promoting malignancy, metastasis, irregular proliferation of cells, and/or their resistance to programmed cell death. Amentoflavone (AMF) is a biflavonoid with intrinsic ability to modulate key signaling pathways associated with homeostatic and non-homeostatic conditions impels its exploration as therapeutic candidate against non-small cell lung carcinoma (NSCLC) A549 cells.
This study investigates the anticancer potential of AMF in A549 cells, focusing on its unique dual role in NF-κB suppression and apoptosis induction, and compares its efficacy to the standard drug doxorubicin.
A549 cells were treated with varying concentrations of AMF for 24 h. The effects of AMF on cell proliferation, oxidative stress, mitochondrial membrane potential, caspase activation, apoptosis, and NF-κB activation was analyzed.
A549 cell viability was substantially reduced (P < 0.001) at an AMF concentration of 60 µM. AMF exposure further increased nuclear fragmentation and condensation in A549 cells. AMF treatment induced apoptosis with concomitant augmentation intracellular production of reactive oxygen species (ROS), dissipation of mitochondrial membrane potential, and activation of the caspase cascade. Additionally, AMF mediated the inhibition of NF-κB and modulated the expression of NF-κB-associated genes involved in cell survival (Bcl-XL, Bcl-2, and survivin) and proliferation (cyclinD1). These results were further supported by in silico studies, which demonstrated a considerable binding energy score of AMF with NF-κB p65/50 compared with the standard drug (doxorubicin).
Thus, it was concluded that AMF exerts potent anticancer effects in NSCLC A549 cells through dual mechanism such as direct inhibition of NF-κB signaling and apoptosis induction combined with its high binding affinity, positions it as a promising therapeutic candidate for NSCLC. Further preclinical studies are warranted to validate these findings.
肺癌是全球癌症发病率和死亡率的主要贡献因素。核因子κB（NF-κB）的慢性激活会触发其靶基因的激活，这些靶基因参与促进恶性肿瘤、转移、细胞的不规则增殖和/或它们对程序性细胞死亡的抗性。穗花杉双黄酮（AMF）是一种双黄酮，具有调节与稳态和非稳态条件相关的关键信号通路的内在能力，促使其作为抗非小细胞肺癌（NSCLC）A549细胞的治疗候选物进行探索。
本研究调查AMF对A549细胞的抗癌潜力，重点关注其在抑制NF-κB和诱导凋亡方面的独特双重作用，并将其疗效与标准药物阿霉素进行比较。
用不同浓度的AMF处理A549细胞24小时。分析AMF对细胞增殖、氧化应激、线粒体膜电位、半胱天冬酶激活、凋亡和NF-κB激活的影响。
在AMF浓度为60μM时，A549细胞活力显著降低（P<0.001）。AMF暴露进一步增加了A549细胞中的核碎片化和凝聚。AMF处理诱导凋亡，同时细胞内活性氧（ROS）产生增加、线粒体膜电位耗散和半胱天冬酶级联激活。此外，AMF介导对NF-κB的抑制，并调节参与细胞存活（Bcl-XL、Bcl-2和存活素）和增殖（细胞周期蛋白D1） 的NF-κB相关基因的表达。计算机模拟研究进一步支持了这些结果，该研究表明与标准药物（阿霉素）相比，AMF与NF-κB p65/50具有相当高的结合能得分。
因此，得出结论，AMF通过直接抑制NF-κB信号传导和诱导凋亡等双重机制在NSCLC A549细胞中发挥强大的抗癌作用，再加上其高结合亲和力，使其成为NSCLC有前景的治疗候选物。需要进一步的临床前研究来验证这些发现。
