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Anticancer properties and mechanism of action of the quassinoid ailanthone
Phytotherapy Research ( IF 6.1 ) Pub Date : 2020-04-01 , DOI: 10.1002/ptr.6681
Christian Bailly 1
Affiliation  

Ailanthone (AIT) is a quassinoid natural product isolated from the worldwide‐distributed plant Ailanthus altissima. The drug displays multiple pharmacological properties, in particular significant antitumor effects against a variety of cancer cell lines in vitro. Potent in vivo activities have been evidenced in mice bearing hepatocellular carcinoma, nonsmall cell lung cancer and castration‐resistant prostate cancer. This review focusses on the mechanism of action of AIT, notably to highlight the capacity of the drug to activate DNA damage responses, to inhibit the Hsp90 co‐chaperone p23 and to modulate the expression of several microRNA. The interconnexion between these effects is discussed. The unique capacity of AIT to downregulate oncogenic miR‐21 and to upregulate the tumor suppressor miRNAs miR‐126, miR‐148a, miR‐195, and miR‐449a is presented. AIT exploits several microRNAs to exert its anticancer effects in distinct tumor types. AIT is one of the rare antitumor natural products that binds to and strongly inhibits cochaperone p23, opening interesting perspectives to treat cancers. However, the toxicity profile of the molecule may limit its development as an anticancer drug, unless it can be properly formulated to prevent AIT‐induced gastro‐intestinal damages in particular. The antitumor properties of AIT and analogs are underlined, with the aim to encourage further pharmacological studies with this underexplored natural product and related quassinoids.

中文翻译:

类苦参素臭椿酮的抗癌特性和作用机制

臭臭酮 (AIT) 是一种从世界范围内分布的植物臭椿中分离出来的类苦参天然产物。该药物显示出多种药理特性,尤其是在体外对多种癌细胞系具有显着的抗肿瘤作用。在携带肝细胞癌、非小细胞肺癌和去势抵抗性前列腺癌的小鼠中已经证明了有效的体内活性。本综述重点关注 AIT 的作用机制,特别是强调药物激活 DNA 损伤反应、抑制 Hsp90 共伴侣 p23 和调节几种 microRNA 表达的能力。讨论了这些效应之间的相互联系。AIT 下调致癌 miR-21 和上调肿瘤抑制 miRNA miR-126、miR-148a、miR-195 的独特能力,和 miR-449a 出现。AIT 利用几种 microRNA 在不同的肿瘤类型中发挥其抗癌作用。AIT 是一种罕见的抗肿瘤天然产物,可结合并强烈抑制辅伴侣 p23,为治疗癌症开辟了有趣的前景。然而,该分子的毒性特征可能会限制其作为抗癌药物的发展,除非它可以适当地配制以防止 AIT 引起的胃肠道损伤。强调了 AIT 和类似物的抗肿瘤特性,目的是鼓励对这种未充分探索的天然产物和相关类拟甙元进行进一步的药理学研究。开辟治疗癌症的有趣视角。然而,该分子的毒性特征可能会限制其作为抗癌药物的发展,除非它可以适当地配制以防止 AIT 引起的胃肠道损伤。强调了 AIT 和类似物的抗肿瘤特性,目的是鼓励对这种未充分探索的天然产物和相关类拟甙元进行进一步的药理学研究。开辟治疗癌症的有趣视角。然而,该分子的毒性特征可能会限制其作为抗癌药物的发展,除非它可以适当地配制以防止 AIT 引起的胃肠道损伤。强调了 AIT 和类似物的抗肿瘤特性,目的是鼓励对这种未充分探索的天然产物和相关类拟甙元进行进一步的药理学研究。
更新日期:2020-04-01
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