Marine Mollusk-Derived Agents with Antiproliferative Activity as Promising Anticancer Agents to Overcome Chemotherapy Resistance.
Marine Mollusk-Derived Agents with Antiproliferative Activity as Promising Anticancer Agents to Overcome Chemotherapy Resistance.
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DOI：
10.1002/med.21423
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发表时间：
2017-07
影响因子：
13.3
通讯作者：
Kiss R
中科院分区：
文献类型：
--
作者：
Ciavatta ML;Lefranc F;Carbone M;Mollo E;Gavagnin M;Betancourt T;Dasari R;Kornienko A;Kiss R
对海洋软体动物的化学研究已导致分离出广泛的生物活性代谢物，它们在海洋生物中进化为在不同环境中生存的良好适应能力。它们中的大多数来自食物来源，但也可以由软体动物本身生物合成，或由共生体产生。因此，分离出的化合物不能严格地视为不同软体动物物种的“化学分类标记”。然而，对这一门的化学研究提供了许多感兴趣的化合物作为潜在的抗癌药物，鉴于不断增长的癌症生物学和化疗文献，这些化合物具有特别重要的意义。目前的综述强调了化学结构、作用机制的多样性，最重要的是，软体动物来源的代谢物作为抗癌药物的潜力，包括那些由软体动物生物合成的代谢物和那些来自饮食的代谢物。在讨论了之前在临床试验中研究的Dolastatins和Kahalalide化合物后，综述涵盖了潜在的有前景的抗癌药物，根据其结构类型进行了分类，包括萜类、类固醇、多肽、多酮和含氮化合物。软体动物来源的天然产品作为抗癌剂的“前景”是根据其针对导致治疗结果不佳的癌细胞的生物学特征的能力进行评估的。这些特点包括体外对癌细胞的高抗增殖能力，对癌细胞增殖的优先抑制，通过非凋亡信号通路的作用机制，规避多药耐药表型，以及体内高活性等。审查还包括关于软体动物衍生抗癌药物的定向递送及其数量采购解决方案的章节。
The chemical investigation of marine mollusks has led to the isolation of a wide variety of bioactive metabolites, which evolved in marine organisms as favorable adaptations to survive in different environments. Most of them are derived from food sources, but they can be also biosynthesized de novo by the mollusks themselves, or produced by symbionts. Consequently, the isolated compounds cannot be strictly considered as “chemotaxonomic markers” for the different molluscan species. However, the chemical investigation of this phylum has provided many compounds of interest as potential anticancer drugs that assume particular importance in the light of the growing literature on cancer biology and chemotherapy. The current review highlights the diversity of chemical structures, mechanisms of action, and, most importantly, the potential of mollusk‐derived metabolites as anticancer agents, including those biosynthesized by mollusks and those of dietary origin. After the discussion of dolastatins and kahalalides, compounds previously studied in clinical trials, the review covers potentially promising anticancer agents, which are grouped based on their structural type and include terpenes, steroids, peptides, polyketides and nitrogen‐containing compounds. The “promise” of a mollusk‐derived natural product as an anticancer agent is evaluated on the basis of its ability to target biological characteristics of cancer cells responsible for poor treatment outcomes. These characteristics include high antiproliferative potency against cancer cells in vitro, preferential inhibition of the proliferation of cancer cells over normal ones, mechanism of action via nonapoptotic signaling pathways, circumvention of multidrug resistance phenotype, and high activity in vivo, among others. The review also includes sections on the targeted delivery of mollusk‐derived anticancer agents and solutions to their procurement in quantity.