Varghese Elizabeth, Samuel Samson Mathews, Abotaleb Mariam, Cheema Sohaila, Mamtani Ravinder, Büsselberg Dietrich
Department of Physiology and Biophysics, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha 24144, Qatar.
Institute for Population Health, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha 24144, Qatar.
Cancers (Basel). 2018 Sep 21;10(10):346. doi: 10.3390/cancers10100346.
Among the different types of breast cancers, triple-negative breast cancers (TNBCs) are highly aggressive, do not respond to conventional hormonal/human epidermal growth factor receptor 2 (HER2)-targeted interventions due to the lack of the respective receptor targets, have chances of early recurrence, metastasize, tend to be more invasive in nature, and develop drug resistance. The global burden of TNBCs is increasing regardless of the number of cytotoxic drugs being introduced into the market each year as they have only moderate efficacy and/or unforeseen side effects. Therefore, the demand for more efficient therapeutic interventions, with reduced side effects, for the treatment of TNBCs is rising. While some plant metabolites/derivatives actually induce the risk of cancers, many plant-derived active principles have gained attention as efficient anticancer agents against TNBCs, with fewer adverse side effects. Here we discuss the possible oncogenic molecular pathways in TNBCs and how the purified plant-derived natural compounds specifically target and modulate the genes and/or proteins involved in these aberrant pathways to exhibit their anticancer potential. We have linked the anticancer potential of plant-derived natural compounds (luteolin, chalcones, piperine, deguelin, quercetin, rutin, fisetin, curcumin, resveratrol, and others) to their ability to target multiple dysregulated signaling pathways (such as the Wnt/β-catenin, Notch, NF-κB, PI3K/Akt/mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (MAPK) and Hedgehog) leading to suppression of cell growth, proliferation, migration, inflammation, angiogenesis, epithelial-mesenchymal transition (EMT) and metastasis, and activation of apoptosis in TNBCs. Plant-derived compounds in combination with classical chemotherapeutic agents were more efficient in the treatment of TNBCs, possibly with lesser side effects.
在不同类型的乳腺癌中，三阴性乳腺癌（TNBC）具有高度侵袭性，由于缺乏相应的受体靶点，对传统的激素/人表皮生长因子受体2（HER2）靶向干预无反应，有早期复发、转移的风险，本质上往往更具侵袭性，且会产生耐药性。尽管每年都有细胞毒性药物进入市场，但由于其疗效一般和/或存在不可预见的副作用，TNBC的全球负担仍在增加。因此，对更有效且副作用更小的TNBC治疗干预措施的需求正在上升。虽然一些植物代谢物/衍生物实际上会诱发癌症风险，但许多植物源活性成分作为针对TNBC的高效抗癌剂受到关注，且副作用较少。在此，我们讨论TNBC中可能的致癌分子途径，以及纯化的植物源天然化合物如何特异性靶向并调节参与这些异常途径的基因和/或蛋白质，以展现其抗癌潜力。我们将植物源天然化合物（木犀草素、查耳酮、胡椒碱、鱼藤素、槲皮素、芦丁、非瑟酮、姜黄素、白藜芦醇等）的抗癌潜力与其靶向多种失调信号通路（如Wnt/β-连环蛋白、Notch、NF-κB、PI3K/Akt/雷帕霉素哺乳动物靶蛋白（mTOR）、丝裂原活化蛋白激酶（MAPK）和Hedgehog）的能力联系起来，这些信号通路可导致TNBC中细胞生长、增殖、迁移、炎症、血管生成、上皮-间质转化（EMT）和转移受到抑制，并激活细胞凋亡。植物源化合物与经典化疗药物联合使用在TNBC治疗中更有效，且可能副作用更小。
