苦楝（Azadirachta indica A. Juss.）是一种多用途的常绿树，以其民族药理学价值而闻名，是富含具有强效药用性能的三萜类柠檬内酯的重要来源。已记载苦楝提取物在不同恶性细胞系和临床前动物模型中表现出抗癌效应，这主要归因于其成分柠檬内酯。近来，苦楝柠檬内酯作为潜在的癌症预防和治疗候选药物，受到了研究的关注。在苦楝中发现的多种柠檬内酯中，阿扎脱尔胞苷、环氧阿扎脱尔二酮、吉敦苑和尼伯利德已广泛研究其抗癌活性。阿扎脱尔胞苷是一种强效的可生物降解杀虫剂，通过阻断有丝分裂纺锤体形成和细胞分裂，表现出深远的抗增殖效应。吉敦苑的抗增殖活性主要通过抑制热休克蛋白90及其客体蛋白的作用介导。环氧阿扎脱尔二酮通过抑制促炎和激酶驱动的信号通路来阻断肿瘤发生。尼伯利德是最强效的细胞毒性苦楝柠檬内酯，通过调节驱动癌症信号的关键激酶的磷酸化，并调节表观基因组，抑制癌细胞生长。有压倒性的证据表明，苦楝柠檬内酯通过防止癌症的典型特征的获得，如细胞增殖、逃逸凋亡、炎症、侵袭、血管生成和耐药性，发挥抗癌效应。苦楝柠檬内酯是靶向异常癌基因信号传导以抑制癌症发展和进展的天然化合物库中的重要补充。© 2023 Wiley Periodicals LLC.

Neem (Azadirachta indica A. Juss.), a versatile evergreen tree recognized for its ethnopharmacological value, is a rich source of limonoids of the triterpenoid class, endowed with potent medicinal properties. Extracts of neem have been documented to display anticancer effects in diverse malignant cell lines as well as in preclinical animal models that has largely been attributed to the constituent limonoids. Of late, neem limonoids have become the cynosure of research attention as potential candidate agents for cancer prevention and therapy. Among the various limonoids found in neem, azadirachtin, epoxyazadiradione, gedunin, and nimbolide, have been extensively investigated for anticancer activity. Azadirachtin, a potent biodegradable pesticide, exhibits profound antiproliferative effects by preventing mitotic spindle formation and cell division. The antiproliferative activity of gedunin has been demonstrated to be mediated primarily via inhibition of heat shock protein90 and its client proteins. Epoxyazadiradione inhibits pro-inflammatory and kinase-driven signaling pathways to block tumorigenesis. Nimbolide, the most potent cytotoxic neem limonoid, inhibits the growth of cancer cells by regulating the phosphorylation of keystone kinases that drive oncogenic signaling besides modulating the epigenome. There is overwhelming evidence to indicate that neem limonoids exert anticancer effects by preventing the acquisition of hallmark traits of cancer, such as cell proliferation, apoptosis evasion, inflammation, invasion, angiogenesis, and drug resistance. Neem limonoids are value additions to the armamentarium of natural compounds that target aberrant oncogenic signaling to inhibit cancer development and progression.© 2023 Wiley Periodicals LLC.