Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Denver, Aurora, CO 80045, USA.
Cancer Metastasis Rev. 2010 Sep;29(3):447-63. doi: 10.1007/s10555-010-9237-0.
Cancer is a major health problem around the world. Research efforts in the last few decades have been successful in providing better and effective treatments against both early stage and localized cancer, but clinical options against advanced metastatic stage/s of cancer remain limited. The high morbidity and mortality in most of the cancers are attributed to their metastatic spread to distant organs. Due to its extreme clinical relevance, metastasis has been extensively studied and is now understood as a highly complex biological event that involves multiple steps including acquisition of invasiveness by cancer cells, intravasation into circulatory system, survival in the circulation, arrest in microvasculature, extravasation, and growth at distant organs. The increasing understanding of molecular underpinnings of these events has provided excellent opportunity to target metastasis especially through nontoxic and biologically effective nutraceuticals. Silibinin, a popular dietary supplement isolated from milk thistle seed extracts, is one such natural agent that has shown biological efficacy through pleiotropic mechanisms against a variety of cancers and is currently in clinical trials. Recent preclinical studies have also shown strong efficacy of silibinin to target cancer cell's migratory and invasive characteristics as well as their ability to metastasize to distant organs. Detailed mechanistic analyses revealed that silibinin targets signaling molecules involved in the regulation of epithelial-to-mesenchymal transition, proteases activation, adhesion, motility, invasiveness as well as the supportive tumor-microenvironment components, thereby inhibiting metastasis. Overall, the long history of human use, remarkable nontoxicity, and preclinical efficacy strongly favor the clinical use of silibinin against advanced metastatic cancers.
癌症是全球主要的健康问题。在过去几十年的研究努力中，针对早期和局部癌症的治疗方法已经取得了成功，但针对晚期转移性癌症的临床选择仍然有限。大多数癌症的高发病率和死亡率归因于其向远处器官的转移扩散。由于其具有极高的临床相关性，转移已被广泛研究，现在被理解为一个涉及多个步骤的高度复杂的生物学事件，包括癌细胞获得侵袭性、进入循环系统、在循环系统中存活、在微血管中停滞、渗出以及在远处器官生长。对这些事件的分子基础的深入了解为靶向转移提供了极好的机会，特别是通过非毒性和具有生物效应的营养保健品。水飞蓟素是一种从奶蓟种子提取物中分离出来的流行膳食补充剂，就是这样一种天然药物，它通过多种机制对各种癌症表现出生物疗效，目前正在临床试验中。最近的临床前研究还表明，水飞蓟素对靶向癌细胞的迁移和侵袭特性以及它们向远处器官转移的能力具有很强的疗效。详细的机制分析表明，水飞蓟素靶向参与上皮间质转化、蛋白酶激活、黏附、运动、侵袭以及支持肿瘤微环境成分调节的信号分子，从而抑制转移。总的来说，水飞蓟素在人类使用的悠久历史、显著的非毒性和临床前疗效强烈支持其在临床上用于治疗晚期转移性癌症。
