INSERM, U866, 21079, Dijon, France.
Cell Mol Life Sci. 2010 Sep;67(18):3115-30. doi: 10.1007/s00018-010-0407-6. Epub 2010 May 29.
TNF-related apoptosis-inducing ligand (TRAIL) and its receptors are attractive targets for anticancer therapy owing to their ability to trigger apoptosis selectively in cancer cells but not in normal cells. To date, many combinatorial strategies, such as chemotherapy or radiotherapy, have given encouraging results for overcoming TRAIL resistance in preclinical models. In this review, we provide an overview of the molecular mechanisms underlying sensitization to TRAIL-induced apoptosis by polyphenols. These naturally occurring compounds can restore tumor cell sensitivity to TRAIL-induced cell death with no apparent toxicity towards normal cells. Both extrinsic and intrinsic pathways can be modulated by polyphenols, the activation of which largely depends on the cell type, the particular polyphenolic compound, and the conditions of treatment. The large variety of polyphenol cellular targets could prove useful in circumventing TRAIL resistance. The relevance of these combined treatments for cancer therapy is discussed in the light of recent preclinical studies.
肿瘤坏死因子相关凋亡诱导配体（TRAIL）及其受体因其能够选择性地在癌细胞中引发凋亡而在正常细胞中不引发凋亡，因此成为癌症治疗的有吸引力的靶标。迄今为止，许多组合策略，如化疗或放疗，在临床前模型中已经取得了克服 TRAIL 耐药性的令人鼓舞的结果。在这篇综述中，我们概述了多酚诱导 TRAIL 诱导的细胞凋亡的分子机制。这些天然存在的化合物可以恢复肿瘤细胞对 TRAIL 诱导的细胞死亡的敏感性，而对正常细胞没有明显的毒性。多酚可以调节外在和内在途径，其激活在很大程度上取决于细胞类型、特定的多酚化合物和治疗条件。多酚的多种细胞靶标可能有助于规避 TRAIL 耐药性。根据最近的临床前研究，讨论了这些联合治疗在癌症治疗中的相关性。
