文章：

三萜和维甲酸类化合物作为预防和治疗癌症的多功能药物

Triterpenoids and rexinoids as multifunctional agents for the prevention and treatment of cancer

原文发布日期：2007-04-19

DOI: 10.1038/nrc2129

类型: Review Article

开放获取: 否

要点：

1. Synthetic oleanane triterpenoids are a new class of non-cytotoxic and highly multifunctional drugs that have applications for the prevention and treatment of not only cancer, but also of many other diseases with an inflammatory component.
2. Synthetic oleanane triterpenoids are anti-inflammatory and cytoprotective, induce the differentiation of tumour cells, suppress the growth of tumour cells and are effective agents for the induction of apoptosis in cancer cells that are resistant to conventional chemotherapeutic agents.
3. Synthetic oleanane triterpenoids have been shown to be highly effective in many in vivo models for the prevention and treatment of cancer. These studies include the suppression of tumour growth in immunocompromised mice, as well as the prevention of primary lung cancer induced by a chemical carcinogen.
4. Molecular targets of synthetic oleanane triterpenoids include KEAP1 (the inhibitor of the transcription factor, NRF2), IκB kinase, transforming growth factor-β signalling and signal transducer and activator of transcription (STAT) signalling.
5. The molecular mechanism of action of the triterpenoids is believed to be mediated by Michael addition with active nucleophilic groups on proteins, such as the -SH groups on cysteine residues.
6. Rexinoids are molecules that selectively bind to the nuclear receptors known as retinoid X receptors. These receptors interact heterodimerically with many other members of the nuclear steroid receptor superfamily, and therefore have the ability to modulate the action of many steroid-like hormonal agents.
7. Great advances have been made in the synthesis of new rexinoids. These agents are highly potent, non-cytotoxic and do not have many of the toxic effects associated with classical retinoids, making them safer agents to use in the clinic.
8. Both synthetic oleanane triterpenoids and rexinoids exert their effects through multiple signalling pathways and have the potential to be used synergistically to control the inflammatory process, as well as deregulated growth associated with cancer.

要点翻译：

1. 合成齐墩果烷三萜类化合物是一类新型非细胞毒性多功能药物，不仅可用于防治癌症，还能治疗多种其他炎症相关疾病。
2. 该类化合物具有抗炎和细胞保护作用，能诱导肿瘤细胞分化、抑制肿瘤细胞生长，并能有效诱导对常规化疗药物耐药的癌细胞凋亡。
3. 在多种体内模型中，合成齐墩果烷三萜类化合物被证实对癌症防治具有显著效果，包括抑制免疫缺陷小鼠的肿瘤生长，以及预防化学致癌物诱发的原发性肺癌。
4. 其分子靶点包括KEAP1（转录因子NRF2的抑制蛋白）、IκB激酶、转化生长因子-β信号通路及STAT信号通路。
5. 这类三萜化合物的分子作用机制被认为是通过与蛋白质亲核基团（如半胱氨酸残基的巯基）发生迈克尔加成反应来实现的。
6. 瑞克素类化合物能选择性结合视黄醇X核受体。该受体可与核内类固醇受体超家族众多成员形成异源二聚体，从而调控多种类固醇激素的作用。
7. 新型瑞克素类化合物的合成研究取得重大进展，该类制剂具有高效力、非细胞毒性特点，且避免了传统维甲类药物的多重毒副作用，临床使用安全性更高。
8. 合成齐墩果烷三萜类化合物与瑞克素类化合物均通过多信号通路发挥作用，两者在协同调控炎症过程及抑制癌症异常生长方面具有应用潜力。

英文摘要：

Synthetic oleanane triterpenoids and rexinoids are two new classes of multifunctional drugs. They are neither conventional cytotoxic agents, nor are they monofunctional drugs that uniquely target single steps in signal transduction pathways. Synthetic oleanane triterpenoids have profound effects on inflammation and the redox state of cells and tissues, as well as being potent anti-proliferative and pro-apoptotic agents. Rexinoids are ligands for the nuclear receptor transcription factors known as retinoid X receptors. Both classes of agents can prevent and treat cancer in experimental animals. These drugs have unique molecular and cellular mechanisms of action and might prove to be synergistic with standard anti-cancer treatments.

摘要翻译： 

合成齐墩果烷三萜类和维甲酸受体激动剂是两类新型多功能药物。它们既不是传统的细胞毒剂，也不是仅针对信号转导通路中单一环节的单功能药物。合成齐墩果烷三萜类对炎症及细胞与组织的氧化还原状态有深远影响，同时具有强效的抗增殖和促凋亡作用。维甲酸受体激动剂是一类核受体转录因子——维甲酸X受体的配体。这两类药物均能在实验动物中预防和治疗癌症。它们具有独特的分子与细胞作用机制，并可能与标准抗癌治疗产生协同效应。

原文链接：

Triterpenoids and rexinoids as multifunctional agents for the prevention and treatment of cancer