Malik Muhammad Nasir Hayat, Ali Sufyan, Ali Amir, Alanzi Abdullah R, Atif Muhammad, Alharbi Hattan A, Wang Bowen, Raza Moosa, Maqbool Tahir, Anjum Irfan, Jahan Shah, Alshammari Saud O, Solre Gideon F B
Faculty of Pharmacy The University of Lahore Lahore Pakistan.
Department of Pharmacognosy, College of Pharmacy King Saud University Riyadh Saudi Arabia.
Food Sci Nutr. 2025 Jan 6;13(1):e4678. doi: 10.1002/fsn3.4678. eCollection 2025 Jan.
Citronellol (CT) is a naturally occurring lipophilic monoterpenoid which has shown anticancer effects in numerous cancerous cell lines. This study was, therefore, designed to examine CT's potential as an anticancer agent against glioblastoma (GBM). Network pharmacology analysis was employed to identify potential anticancer targets of CT. A comprehensive data mining was carried out to assess CT and GBM-associated target genes. Protein-protein interaction network was constructed to identify hub genes and later GO and KEGG enrichment analysis was performed to elucidate the possible mechanism. Human glioblastoma cell line "SF767" was used to confirm in silico findings. MTT, crystal violet, and trypan blue assays were performed to assess the cytotoxic effects of various concentrations of CT. Subsequently, ELISA and qPCR were performed to analyze the effects of CT on proapoptotic and inflammatory mediators. In silico findings indicated that CT differentially regulated proapoptotic and inflammatory pathways by activating caspase-3 and 8 and inhibiting nuclear factor-kappa B (NF-κB), tumor necrosis factor-α, Janus kinase 2 (JAK2). Molecular docking also demonstrated strong binding affinities of CT with the above-mentioned mediators when compared to 5-fluorouracil or temozolomide. In SF767 cell line, CT displayed dose-dependent cytotoxic and antioxidant effects, and upregulation of annexin-V, caspase-3, and 8 along with downregulation of inflammatory modulators. In a nutshell, it can be concluded from these findings that CT possesses robust anticancer activity which is mediated via differential regulation of caspase-3, JAK2, and NF-κB pathways.
香茅醇（CT）是一种天然存在的亲脂性单萜类化合物，已在众多癌细胞系中显示出抗癌作用。因此，本研究旨在检测CT作为抗胶质母细胞瘤（GBM）抗癌剂的潜力。采用网络药理学分析来确定CT的潜在抗癌靶点。进行了全面的数据挖掘以评估CT和GBM相关的靶基因。构建蛋白质 - 蛋白质相互作用网络以鉴定枢纽基因，随后进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析以阐明可能的机制。使用人胶质母细胞瘤细胞系“SF767”来证实计算机模拟的结果。进行MTT、结晶紫和台盼蓝测定以评估不同浓度CT的细胞毒性作用。随后，进行酶联免疫吸附测定（ELISA）和定量聚合酶链反应（qPCR）以分析CT对促凋亡和炎症介质的影响。计算机模拟结果表明，CT通过激活半胱天冬酶 - 3和8以及抑制核因子 - κB（NF - κB）、肿瘤坏死因子 - α、 Janus激酶2（JAK2）来差异调节促凋亡和炎症途径。与5 - 氟尿嘧啶或替莫唑胺相比，分子对接也证明了CT与上述介质具有很强的结合亲和力。在SF767细胞系中，CT表现出剂量依赖性的细胞毒性和抗氧化作用，膜联蛋白 - V、半胱天冬酶 - 3和8上调以及炎症调节因子下调。简而言之，从这些发现可以得出结论，CT具有强大的抗癌活性，其通过半胱天冬酶 - 3、JAK2和NF - κB途径的差异调节来介导。
