UMRi CNRS 7266 LIENSs, University of La Rochelle, 17042 La Rochelle, France.
Center for Studies and Research of Medicinal Plants, Federal University of San Francisco Valley, 56306-000 Petrolina, Brazil.
Fitoterapia. 2018 Sep;129:383-400. doi: 10.1016/j.fitote.2018.02.025. Epub 2018 Feb 21.
Tumor cells are spontaneously or adaptively resistant to chemotherapeutic drugs, eventually leading to the selection of multiresistant cells responsible for tumor growth and metastasis. Chemosensitization of tumor cells to conventional drugs using non-toxic natural products is a recent and innovative strategy aiming to increase the cytotoxic efficiency of anticancer drugs, limit their toxic side effects and delay the appearance of acquired chemoresistance. This systematic review summarizes data obtained from preclinical studies reporting the use of natural products to sensitize tumor cells to chemotherapeutic agents. It also details the cellular and molecular mechanisms involved in chemosensitization.
Search terms were combined and used to retrieve English language reports in PubMed, Science Direct and Scopus databases, published until October 2017. All articles were carefully analyzed and data extraction was conducted through standardized forms. Methodological quality assessment of in vivo studies was also performed.
From a total of 669 articles surveyed, 104 met the inclusion criteria established. The main studied compounds as chemosensitizers were phenolic derivatives (26.9%) and flavonoids (17.3%). Most reports were authored by researchers from China (33.7%) and USA (26.9%). A large number of articles were published from 2011 to 2015 (50.0%), suggesting that the use of natural products as chemosensitizers is a recent issue. In vivo studies were conducted mainly using xenograft models, which were considered of moderate methodological quality.
Several natural products, belonging to diverse chemical families, are potent chemosentisizers in tumor cells enhancing the cytotoxicity of conventional drugs. These molecules usually have a pleiotropic effect on different molecular targets, acting on several cellular and molecular processes with low selectivity. All studied molecules were obtained from terrestrial plants and major developments should arise from future studies, considering the chemodiversity of molecules purified from other terrestrial taxa and marine organisms.
肿瘤细胞对化疗药物具有自发或适应性耐药性，最终导致负责肿瘤生长和转移的多药耐药细胞的选择。使用无毒的天然产物使肿瘤细胞对常规药物增敏是一种新的策略，旨在提高抗癌药物的细胞毒性效率，限制其毒性副作用，并延迟获得性耐药性的出现。本系统综述总结了来自报告使用天然产物使肿瘤细胞对化疗药物增敏的临床前研究的数据。它还详细介绍了增敏作用涉及的细胞和分子机制。
组合搜索词并用于检索 PubMed、Science Direct 和 Scopus 数据库中截至 2017 年 10 月发表的英文报告。仔细分析所有文章，并通过标准化表格进行数据提取。还对体内研究的方法学质量进行了评估。
从总共调查的 669 篇文章中，有 104 篇符合既定的纳入标准。作为增敏剂的主要研究化合物是酚类衍生物（26.9%）和类黄酮（17.3%）。大多数报告的作者来自中国（33.7%）和美国（26.9%）。大量文章发表于 2011 年至 2015 年（50.0%），表明使用天然产物作为增敏剂是一个新问题。体内研究主要使用异种移植模型进行，这些模型被认为具有中等的方法学质量。
几种天然产物，属于不同的化学家族，是肿瘤细胞中的有效增敏剂，增强了常规药物的细胞毒性。这些分子通常对不同的分子靶标具有多效性作用，对几个细胞和分子过程具有低选择性。所有研究的分子均来自陆地植物，未来的研究应考虑从其他陆地生物和海洋生物中分离纯化的分子的化学多样性，从而取得重大进展。
