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摘要
天然生物活性物质对细胞衰老产生靶向的可能性开启了有趣的治疗癌症与衰老化的视野。在根治癌症上,参与衰老反应被认为是关键的治疗干预部分。同时,延缓衰老或者促进细胞凋亡的抗衰老细胞死亡的积累被作为一种战略去预防与年龄相关的疾病而提出。虽然两个期望的结果呈现一个内在的二分法,还是有例子表明存在满足发展促进营养健康衰老目地的有前景的天然产物。酚类化合物(T3s)和槲皮素(QUE),尽管属于不同的植物类,在正常细胞和肿瘤细胞的“体外”测验中,均表现出相似和有前景的效应。在众多的癌症中,两种化合物都被证明可以诱导衰老和促进细胞凋亡。不同的是,他们展现了原代细胞延缓衰老的活性和衰老细胞的修复作用。最近,在主要的衰老细胞中,槲皮素显示了senolytic效应,可能是在具体的抗凋亡基因(即PI3K和其他激酶)中抑制作用的后果。senolytic效应没有在酚类化合物中测验,但部分的代谢和凋亡通路受在癌症细胞与槲皮素重叠的这些化合物的影响。这说明在衰老和衰老原代细胞中酚类化合物和槲皮素的修复作用可能是衰老细胞的senolytic效应和非衰老细胞亚群的选择性存活作用的综合性结果。文章中讨论了关于用酚类化合物和槲皮素对癌症的辅助治疗及抗衰老的预防策略这一假说的意义。
关键词: 细胞衰老,癌症,Nrf2通路,酚类化合物,槲皮素,内质网应激,senolytic化合物。
Current Drug Targets
Title:Pleiotropic Effects of Tocotrienols and Quercetin on Cellular Senescence: Introducing the Perspective of Senolytic Effects of Phytochemicals
Volume: 17 Issue: 4
Author(s): Marco Malavolta, Elisa Pierpaoli, Robertina Giacconi, Laura Costarelli, Francesco Piacenza and Andrea Basso, Maurizio Cardelli and Mauro Provinciali
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关键词: 细胞衰老,癌症,Nrf2通路,酚类化合物,槲皮素,内质网应激,senolytic化合物。
摘要: The possibility to target cellular senescence with natural bioactive substances open interesting therapeutic perspective in cancer and aging. Engaging senescence response is suggested as a key component for therapeutic intervention in the eradication of cancer. At the same time, delaying senescence or even promote death of accumulating apoptosis-resistant senescent cells is proposed as a strategy to prevent age related diseases. Although these two desired outcome present an intrinsic dichotomy, there are examples of promising natural compounds that appear to satisfy all the requirements to develop senescence- targeted health promoting nutraceuticals. Tocotrienols (T3s) and quercetin (QUE), albeit belonging to different phytochemical classes, display similar and promising effects “in vitro” when tested in normal and cancer cells. Both compounds have been shown to induce senescence and promote apoptosis in a multitude of cancer lines. Conversely, they display senescence delaying activity in primary cells and rejuvenating effects in senescent cells. More recently, QUE has been shown to display senolytic effects in some primary senescent cells, likely as a consequence of its inhibitory effects on specific anti-apoptotic genes (i.e. PI3K and other kinases). Senolytic activity has not been tested for T3s but part of metabolic and apoptotic pathways affected by these compounds in cancer cells overlap with those of QUE. This suggests that the rejuvenating effects of T3s and QUE on pre-senescent and senescent primary cells might be the net results of a senolytic activity on senescent cells and a selective survival of a sub-population of non-senescent cells in the culture. The meaning of this hypothesis in the context of adjuvant therapy of cancer and preventive anti-aging strategies with QUE or T3s is discussed.
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Marco Malavolta, Elisa Pierpaoli, Robertina Giacconi, Laura Costarelli, Francesco Piacenza and Andrea Basso, Maurizio Cardelli and Mauro Provinciali , Pleiotropic Effects of Tocotrienols and Quercetin on Cellular Senescence: Introducing the Perspective of Senolytic Effects of Phytochemicals, Current Drug Targets 2016; 17 (4) . https://dx.doi.org/10.2174/1389450116666150907105104
DOI https://dx.doi.org/10.2174/1389450116666150907105104 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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