Advanced Technology Center for Aging Research, Scientific Technological Area, Italian National Institute of Health and Science on Aging (INRCA), Ancona 60121, Italy.
Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Ancona 60126, Italy.
Mediators Inflamm. 2018 Feb 12;2018:4159013. doi: 10.1155/2018/4159013. eCollection 2018.
The reactivation of senescence in cancer and the subsequent clearance of senescent cells are suggested as therapeutic intervention in the eradication of cancer. Several natural compounds that activate Nrf2 (nuclear factor erythroid-derived 2-related factor 2) pathway, which is involved in complex cytoprotective responses, have been paradoxically shown to induce cell death or senescence in cancer. Promoting the cytoprotective Nrf2 pathway may be desirable for chemoprevention, but it might be detrimental in later stages and advanced cancers. However, senolytic activity shown by some Nrf2-activating compounds could be used to target senescent cancer cells (particularly in aged immune-depressed organisms) that escape immunosurveillance. We herein describe in vitro and in vivo effects of fifteen Nrf2-interacting natural compounds (tocotrienols, curcumin, epigallocatechin gallate, quercetin, genistein, resveratrol, silybin, phenethyl isothiocyanate, sulforaphane, triptolide, allicin, berberine, piperlongumine, fisetin, and phloretin) on cellular senescence and discuss their use in adjuvant cancer therapy. In light of available literature, it can be concluded that the meaning and the potential of adjuvant therapy with natural compounds in humans remain unclear, also taking into account the existence of few clinical trials mostly characterized by uncertain results. Further studies are needed to investigate the therapeutic potential of those compounds that display senolytic activity.
衰老细胞的再激活以及随后衰老细胞的清除被认为是消除癌症的一种治疗干预手段。几种激活 Nrf2（核因子红细胞 2 相关因子 2）途径的天然化合物，该途径参与复杂的细胞保护反应，被证明具有诱导癌细胞死亡或衰老的作用。促进细胞保护 Nrf2 途径可能有利于化学预防，但在晚期和晚期癌症中可能有害。然而，一些 Nrf2 激活化合物表现出的衰老细胞选择性活性可用于靶向衰老的癌细胞（特别是在衰老的免疫抑制机体中），这些细胞逃避免疫监视。本文描述了十五种 Nrf2 相互作用的天然化合物（生育三烯酚、姜黄素、表没食子儿茶素没食子酸酯、槲皮素、染料木黄酮、白藜芦醇、水飞蓟素、苯乙基异硫氰酸酯、萝卜硫素、雷公藤甲素、大蒜素、小檗碱、胡椒碱、非瑟酮和根皮苷）在细胞衰老中的体外和体内效应，并讨论了它们在辅助癌症治疗中的应用。根据现有文献，可以得出结论，考虑到很少有临床试验，且这些临床试验的结果大多不确定，这些临床试验在人类中使用天然化合物进行辅助治疗的意义和潜力仍不清楚。需要进一步的研究来调查那些具有衰老细胞选择性活性的化合物的治疗潜力。
