Teaching and Research Division, School of Chinese Medicine, Hong Kong Baptist University, 7 Baptist University Road, Kowloon Tong, Kowloon, Hong Kong.
Department of Pharmacy, East West University, Dhaka, Bangladesh.
Eur J Pharmacol. 2022 Aug 5;928:174991. doi: 10.1016/j.ejphar.2022.174991. Epub 2022 May 2.
During the last few decades, cancer has remained one of the deadliest diseases that endanger human health, emphasizing urgent drug discovery. Cellular senescence has gained a great deal of attention in recent years because of its link to the development of cancer therapy. Senescent cells are incapable of proliferating due to irreversibly inhibition of the initiation of the cell cycle pathways. However, senescent cells aggregate in tissues and produce a pro-inflammatory secretome called senescence-associated secretory phenotype (SASP) that can cause serious harmful effects if not managed properly. There is mounting evidence that senescent cells lead to various phases of tumorigenesis in various anatomical sites, owing mostly to the paracrine activities of the SASP. Therefore, a new treatment field called senotherapeutics has been established. Senotherapeutics are newly developed anticancer agents that have been demonstrated to inhibit cancer efficiently. In light of recent findings, several promising natural products have been identified as senescence inducers and senotherapeutics, including, miliusanes, epigallocatechin gallate, phloretin, silybin, resveratrol, genistein, sulforaphane, quercetin, allicin, fisetin, piperlongumine, berberine, triptolide, tocotrienols and curcumin analogs. Some of them have already been validated through preclinical trials and exert an enormous potential for clinical trials. This review article focuses on and summarizes the latest advances made on cellular senescence and its potential as a target for cancer treatment and highlights the well-known natural products as senescence inducers and senotherapeutics for cancer treatment.
在过去的几十年中，癌症一直是威胁人类健康的最致命疾病之一，强调急需药物发现。近年来，细胞衰老因其与癌症治疗的发展有关而受到极大关注。衰老细胞由于不可逆地抑制细胞周期途径的启动而无法增殖。然而，衰老细胞在组织中聚集并产生一种称为衰老相关分泌表型（SASP）的促炎分泌组，如果处理不当，可能会造成严重的有害影响。越来越多的证据表明，衰老细胞导致各种解剖部位的肿瘤发生的各个阶段，主要是由于 SASP 的旁分泌活性。因此，建立了一个名为衰老治疗学的新治疗领域。衰老治疗学是新开发的抗癌药物，已被证明能有效地抑制癌症。鉴于最近的发现，已经确定了几种有前途的天然产物作为衰老诱导剂和衰老治疗剂，包括米利乌萨内斯、表没食子儿茶素没食子酸酯、根皮苷、水飞蓟素、白藜芦醇、染料木黄酮、萝卜硫素、槲皮素、大蒜素、漆黄素、胡椒碱、小檗碱、雷公藤内酯、生育三烯酚和姜黄素类似物。其中一些已经通过临床前试验得到验证，并具有巨大的临床试验潜力。本文综述了细胞衰老及其作为癌症治疗靶点的最新进展，并强调了一些著名的天然产物作为衰老诱导剂和衰老治疗剂在癌症治疗中的应用。
