Abdallah Rola, Shaito Abdullah A, Badran Adnan, Baydoun Serine, Sobeh Mansour, Ouchari Wafae, Sahri Nihad, Eid Ali H, Mesmar Joelle Edward, Baydoun Elias
Department of Biology, American University of Beirut, Beirut, Lebanon.
Biomedical Research Center, Department of Biomedical Sciences at College of Health Sciences, and College of Medicine, Qatar University, Doha, Qatar.
Front Pharmacol. 2024 Feb 9;15:1331843. doi: 10.3389/fphar.2024.1331843. eCollection 2024.
Natural products have long been utilized in traditional medicine as remedies to improve health and treat illnesses, and have had a key role in modern drug discovery. Recently, there has been a revived interest in the search for bioactives from natural sources as alternative or complementary modalities to synthetic medicines; especially for cancer treatment, which incidence and mortality rates are on the rise worldwide. has been widely used in traditional medicine for the treatment of various diseases. Its traditional uses and numerous ethnopharmacological properties may be attributed to its richness in bioactive metabolites. However, its phytochemical composition or chemopreventive effects against the aggressive triple-negative breast cancer (TNBC) are still poorly explored. Here, phytochemical composition of an ethanolic extract of leaves (ZNE) and its chromatographically isolated fractions was identified both qualitatively by spectrophotometric assays and analytically by HPLC-PDA-MS/MS. The anti-proliferative effects of ZNE were tested in several cancer cell lines, but we focused on its anti-TNBC effects since they were not explored yet. The anti-cancerous potential of ZNE and its fractions was tested in MDA-MB-231, a TNBC cell line. Results showed that ZNE and its Fraction 6 (F6) reduced the viability of MDA-MB-231 cells. F6 decreased MDA-MB-231 viability more than crude ZNE or its other fractions. ZNE and F6 are rich in phytochemicals and HPLC-PDA-MS/MS analysis identified several metabolites that were previously reported to have anti-cancerous effects. Both ZNE and F6 showed potent antioxidant capacity in the DPPH assay, but promoted reactive oxygen species (ROS) production in MDA-MB-231 cells; an effect which was blunted by the antioxidant N-acetyl cysteine (NAC). NAC also blunted ZNE- and F6-induced reduction in TNBC cell viability. We also demonstrated that ZNE and F6 induced an arrest of the cell cycle, and triggered apoptosis- and autophagy-mediated cell death. ZNE and F6 inhibited metastasis-related cellular processes by modifying cell migration, invasion, and adhesion. Taken together, our findings reveal that . is rich in phytochemicals that can attenuate the malignant phenotype of TNBC and may offer innovative avenues for the discovery of new drug leads for treatment of TNBC and other cancers.
天然产物长期以来一直被用于传统医学，作为改善健康和治疗疾病的药物，并且在现代药物发现中发挥了关键作用。最近，人们对从天然来源寻找生物活性物质作为合成药物的替代或补充方式重新产生了兴趣；特别是对于癌症治疗，全球范围内其发病率和死亡率都在上升。 已被广泛用于传统医学治疗各种疾病。其传统用途和众多民族药理学特性可能归因于其丰富的生物活性代谢产物。然而，其植物化学成分或对侵袭性三阴性乳腺癌（TNBC）的化学预防作用仍未得到充分探索。在这里，通过分光光度法测定对 叶乙醇提取物（ZNE）及其色谱分离组分的植物化学成分进行了定性鉴定，并通过HPLC-PDA-MS/MS进行了分析鉴定。在几种癌细胞系中测试了ZNE的抗增殖作用，但由于尚未对其抗TNBC作用进行探索，我们将重点放在了这方面。在TNBC细胞系MDA-MB-231中测试了ZNE及其组分的抗癌潜力。结果表明，ZNE及其组分6（F6）降低了MDA-MB-231细胞的活力。F6比粗制ZNE或其其他组分更能降低MDA-MB-231细胞的活力。ZNE和F6富含植物化学成分，HPLC-PDA-MS/MS分析鉴定出几种先前报道具有抗癌作用的代谢产物。ZNE和F-6在DPPH试验中均显示出强大的抗氧化能力，但在MDA-MB-231细胞中促进了活性氧（ROS）的产生；抗氧化剂N-乙酰半胱氨酸（NAC）减弱了这种作用。NAC也减弱了ZNE和F6诱导的TNBC细胞活力降低。我们还证明，ZNE和F6诱导细胞周期停滞，并引发凋亡和自噬介导的细胞死亡。ZNE和F6通过改变细胞迁移、侵袭和黏附来抑制转移相关的细胞过程。综上所述，我们的研究结果表明， 富含可减弱TNBC恶性表型的植物化学成分，并可能为发现治疗TNBC和其他癌症的新药先导物提供创新途径。
