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印楝素,一种印楝柠檬苦素,是抗癌药物库中有前景的候选药物。

Nimbolide, a Neem Limonoid, Is a Promising Candidate for the Anticancer Drug Arsenal.

作者信息

Nagini Siddavaram, Nivetha Ramesh, Palrasu Manikandan, Mishra Rajakishore

机构信息

Department of Biochemistry & Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, Tamil Nadu 608002, India.

Department of Surgery, University of Miami Miller School of Medicine, Rosenstiel Medical Sciences Building, Suite 4116, 1600 NW 10th Avenue, Miami, Florida 33136, United States.

出版信息

J Med Chem. 2021 Apr 8;64(7):3560-3577. doi: 10.1021/acs.jmedchem.0c02239. Epub 2021 Mar 19.

Abstract

Nimbolide, a major limonoid constituent of , commonly known as neem, has attracted increasing research attention owing to its wide spectrum of pharmacological properties, predominantly anticancer activity. Nimbolide is reported to exert potent antiproliferative effects on a myriad cancer cell lines and chemotherapeutic efficacy in preclinical animal tumor models. The potentiality of nimbolide to circumvent multidrug resistance and aid in targeted protein degradation broaden its utility in enhancing therapeutic modalities and outcome. Accumulating evidence indicates that nimbolide prevents the acquisition of cancer hallmarks such as sustained proliferation, apoptosis evasion, invasion, angiogenesis, metastasis, and inflammation by modulating kinase-driven oncogenic signaling networks. Nimbolide has been demonstrated to abrogate aberrant activation of cellular signaling by influencing the subcellular localization of transcription factors and phosphorylation of kinases in addition to influencing the epigenome. Nimbolide, with its ever-expanding repertoire of molecular targets, is a valuable addition to the anticancer drug arsenal.

摘要

印楝素是印楝(俗称苦楝)的一种主要柠檬苦素成分,因其广泛的药理特性,尤其是抗癌活性,已引起越来越多的研究关注。据报道,印楝素对众多癌细胞系具有强大的抗增殖作用,并在临床前动物肿瘤模型中具有化疗效果。印楝素规避多药耐药性和辅助靶向蛋白质降解的潜力拓宽了其在增强治疗方式和疗效方面的应用。越来越多的证据表明,印楝素通过调节激酶驱动的致癌信号网络来阻止癌症特征的获得,如持续增殖、逃避凋亡、侵袭、血管生成、转移和炎症。除了影响表观基因组外,印楝素还通过影响转录因子的亚细胞定位和激酶的磷酸化来消除细胞信号的异常激活。印楝素具有不断扩大的分子靶点库,是抗癌药物库中的宝贵补充。

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