非小细胞肺癌(NSCLC)是一种具有高度异质性的复杂恶性肿瘤,约占所有肺癌病例的85%。通过整合靶向和免疫疗法,NSCLC的治疗领域已经发生了革命性的变化;然而,始终需要新的治疗方式来提高治疗结果.的确,涉及天然产物的替代抗癌疗法由于其非凡的化学预防潜力而引起了临床医生和科学家的注意,通常显示最小的毒性。D-香芹酮(CN)是一种这样的天然产品,表现出许多有希望的治疗益处,然而其对非小细胞肺癌的疗效仍是个谜.在本研究中,通过网络药理学研究和分子对接结合体外验证,全面阐明了CN的潜在作用机制。不同的数据库揭示了总共77个推定的CN抗NSCLC靶标。Cytoscape(v3.9.0)利用所确定的核心靶标构建“复合靶标-疾病”网络。进一步分析确定了CN的5个核心/中心目标,包括JAK2,ERK1,ESR1,GSK3B和HSP90AA1。分子对接表明化合物与这些核心靶标的强结合相互作用。此外,基因本体论和KEGG分析验证了多个生物过程的参与。此外,CN显著抑制细胞增殖,克隆性,和伤口愈合潜力,同时在H1299和A549细胞系中以剂量依赖性方式促进细胞凋亡,如通过流式细胞术检查,形态学评估,和西方印迹。总之,这项研究描述了CN对NSCLC的治疗效果,因此强调CN是进一步分析的推定候选药物。
Non-small cell lung cancer (NSCLC) is a complex malignancy with a high degree of heterogeneity, representing approximately 85% of all lung cancer cases. The treatment landscape for NSCLC has been revolutionised by incorporating targeted and immunotherapies; however, novel therapeutic modalities are consistently needed to enhance the treatment outcomes. Indeed, alternative anti-cancer therapies involving natural products have drawn the attention of clinicians and scientists owing to their remarkable chemopreventive potential, often displaying minimal toxicity. D-carvone (CN) is one such natural product that has exhibited numerous promising therapeutic benefits, yet its efficacy against NSCLC remains enigmatic. In the present
study, network pharmacological studies and molecular docking in conjunction with in-vitro validation were used to elucidate the underlying mechanism of action of CN comprehensively. Different databases revealed a total of 77 putative anti-NSCLC targets of CN. The identified core targets were utilised to construct a \"Compound- Target- Disease\" network by Cytoscape (v3.9.0). Further analysis identified 5 core/ hub targets of CN including JAK2, ERK1, ESR1, GSK3B and HSP90AA1. Molecular docking indicated a strong binding interaction of the compound with these core targets. Also, Gene Ontology and KEGG analysis validated the involvement of multiple biological processes. Additionally, CN significantly inhibited cell proliferation, clonogenicity, and wound healing potential while promoting apoptosis in a dose-dependent manner in H1299 and A549 cell lines as examined by flow cytometry, morphological assessment, and western blotting. In conclusion, this
study delineates the therapeutic effects of CN on NSCLC, thus highlighting CN as a putative drug candidate for further analysis.