Delmas Dominique, Xiao Jianbo, Vejux Anne, Aires Virginie
Université de Bourgogne Franche-Comté, F-21000 Dijon, France.
INSERM Research Center U1231-Cancer and Adaptive Immune Response Team, Dijon, Bioactive Molecules and Health research group, F-21000 Dijon, France.
Molecules. 2020 Apr 25;25(9):2009. doi: 10.3390/molecules25092009.
Silymarin extracted from milk thistle consisting of flavonolignan silybin has shown chemopreventive and chemosensitizing activity against various cancers. The present review summarizes the current knowledge on the potential targets of silymarin against various cancers. Silymarin may play on the system of xenobiotics, metabolizing enzymes (phase I and phase II) to protect normal cells against various toxic molecules or to protect against deleterious effects of chemotherapeutic agents on normal cells. Furthermore, silymarin and its main bioactive compounds inhibit organic anion transporters (OAT) and ATP-binding cassettes (ABC) transporters, thus contributing to counteracting potential chemoresistance. Silymarin and its derivatives play a double role, namely, limiting the progression of cancer cells through different phases of the cycle-thus forcing them to evolve towards a process of cell death-and accumulating cancer cells in a phase of the cell cycle-thus making it possible to target a greater number of tumor cells with a specific anticancer agent. Silymarin exerts a chemopreventive effect by inducing intrinsic and extrinsic pathways and reactivating cell death pathways by modulation of the ratio of proapoptotic/antiapoptotic proteins and synergizing with agonists of death domains receptors. In summary, we highlight how silymarin may act as a chemopreventive agent and a chemosensitizer through multiple pathways.
从水飞蓟中提取的含有黄酮木脂素水飞蓟宾的水飞蓟素已显示出对多种癌症的化学预防和化学增敏活性。本综述总结了目前关于水飞蓟素对各种癌症潜在靶点的认识。水飞蓟素可能作用于外源性物质代谢酶系统（I相和II相），以保护正常细胞免受各种有毒分子的侵害，或防止化疗药物对正常细胞产生有害影响。此外，水飞蓟素及其主要生物活性化合物抑制有机阴离子转运体（OAT）和ATP结合盒（ABC）转运体，从而有助于对抗潜在的化疗耐药性。水飞蓟素及其衍生物发挥双重作用，即通过细胞周期的不同阶段限制癌细胞的进展，从而迫使它们向细胞死亡过程发展，并使癌细胞在细胞周期的某个阶段积累，从而有可能用特定的抗癌药物靶向更多的肿瘤细胞。水飞蓟素通过诱导内在和外在途径以及通过调节促凋亡/抗凋亡蛋白的比例和与死亡结构域受体激动剂协同作用来重新激活细胞死亡途径，从而发挥化学预防作用。总之，我们强调了水飞蓟素如何通过多种途径作为化学预防剂和化学增敏剂发挥作用。
