Drif Assia I, Yücer Rümeysa, Damiescu Roxana, Ali Nadeen T, Abu Hagar Tobias H, Avula Bharati, Khan Ikhlas A, Efferth Thomas
Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany.
National Center for Natural Products Research (NCNPR), School of Pharmacy, University of Mississippi, Oxford, MS 38677, USA.
Biomedicines. 2024 Jul 5;12(7):1484. doi: 10.3390/biomedicines12071484.
Chamomile tea, renowned for its exquisite taste, has been appreciated for centuries not only for its flavor but also for its myriad health benefits. In this study, we investigated the preventive potential of chamomile ( L.) towards cancer by focusing on its anti-inflammatory activity.
A virtual drug screening of 212 phytochemicals from chamomile revealed β-amyrin, β-eudesmol, β-sitosterol, apigenin, daucosterol, and myricetin as potent NF-κB inhibitors. The in silico results were verified through microscale thermophoresis, reporter cell line experiments, and flow cytometric determination of reactive oxygen species and mitochondrial membrane potential. An oncobiogram generated through comparison of 91 anticancer agents with known modes of action using the NCI tumor cell line panel revealed significant relationships of cytotoxic chamomile compounds, lupeol, and quercetin to microtubule inhibitors. This hypothesis was verified by confocal microscopy using α-tubulin-GFP-transfected U2OS cells and molecular docking of lupeol and quercetin to tubulins. Both compounds induced G2/M cell cycle arrest and necrosis rather than apoptosis. Interestingly, lupeol and quercetin were not involved in major mechanisms of resistance to established anticancer drugs (ABC transporters, , or ). Performing hierarchical cluster analyses of proteomic expression data of the NCI cell line panel identified two sets of 40 proteins determining sensitivity and resistance to lupeol and quercetin, further pointing to the multi-specific nature of chamomile compounds. Furthermore, lupeol, quercetin, and β-amyrin inhibited the mRNA expression of the proinflammatory cytokines and in NF-κB reporter cells (HEK-Blue Null1). Moreover, Kaplan-Meier-based survival analyses with NF-κB as the target protein of these compounds were performed by mining the TCGA-based KM-Plotter repository with 7489 cancer patients. Renal clear cell carcinomas (grade 3, low mutational rate, low neoantigen load) were significantly associated with shorter survival of patients, indicating that these subgroups of tumors might benefit from NF-κB inhibition by chamomile compounds.
This study revealed the potential of chamomile, positioning it as a promising preventive agent against inflammation and cancer. Further research and clinical studies are recommended.
洋甘菊茶以其独特的口感而闻名，数百年来一直备受赞赏，不仅因其风味，还因其众多的健康益处。在本研究中，我们通过关注其抗炎活性，研究了洋甘菊对癌症的预防潜力。
对来自洋甘菊的212种植物化学物质进行虚拟药物筛选，发现β-香树脂醇、β-桉叶醇、β-谷甾醇、芹菜素、胡萝卜苷和杨梅素是有效的NF-κB抑制剂。通过微量热泳、报告细胞系实验以及活性氧和线粒体膜电位的流式细胞术测定，验证了计算机模拟结果。通过使用NCI肿瘤细胞系面板将91种已知作用模式的抗癌药物进行比较生成的肿瘤生物学图谱显示，具有细胞毒性的洋甘菊化合物羽扇豆醇和槲皮素与微管抑制剂有显著关系。使用α-微管蛋白-GFP转染的U2OS细胞进行共聚焦显微镜检查以及羽扇豆醇和槲皮素与微管蛋白的分子对接，验证了这一假设。这两种化合物均诱导G2/M期细胞周期停滞和坏死而非凋亡。有趣的是，羽扇豆醇和槲皮素不参与对已确立的抗癌药物（ABC转运蛋白等）的主要耐药机制。对NCI细胞系面板的蛋白质组表达数据进行层次聚类分析，确定了两组共40种蛋白质，它们决定了对羽扇豆醇和槲皮素的敏感性和耐药性，进一步表明洋甘菊化合物具有多特异性。此外，羽扇豆醇、槲皮素和β-香树脂醇抑制了NF-κB报告细胞（HEK-Blue Null1）中促炎细胞因子和的mRNA表达。此外，以NF-κB作为这些化合物的靶蛋白，通过挖掘基于TCGA的KM-Plotter数据库中7489名癌症患者的数据，进行了基于Kaplan-Meier的生存分析。肾透明细胞癌（3级，低突变率，低新抗原负荷）与患者较短的生存期显著相关，表明这些肿瘤亚组可能受益于洋甘菊化合物对NF-κB的抑制作用。
本研究揭示了洋甘菊的潜力，将其定位为一种有前景的抗炎和抗癌预防剂。建议进一步开展研究和临床研究。
