Isoflavonoids from Brazilian red propolis down-regulate the expression of cancer-related target proteins: A pharmacogenomic analysis.
Isoflavonoids from Brazilian red propolis down-regulate the expression of cancer-related target proteins: A pharmacogenomic analysis.
复制标题
巴西红蜂胶中的异黄酮类化合物下调癌症相关靶蛋白的表达：药物基因组学分析。
DOI：
10.1002/ptr.6016
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Rosalen,PedroLuiz
中科院分区：
文献类型：
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作者：
Nani,BrunoDias;Franchin,Marcelo;Lazarini,JosyGoldoni;Freires,IrlanAlmeida;daCunha,MarcosGuilherme;Bueno-Silva,Bruno;deAlencar,SeverinoMatias;Murata,RamiroMendonça;Rosalen,PedroLuiz
摘要西炔雌醇和新西炔雌醇是从巴西红蜜蜂中分离得到的具有生物活性的化合物。尽管这些分子具有相关的生物学效应，包括抗癌和免疫调节活性，但其作用机制和受影响的途径在很大程度上仍然未知。在这里，我们进行了药物基因组学分析，以研究vestitol和neovestitol对人类肿瘤细胞中全基因组表达的影响，特别是癌症相关的靶蛋白。将HeLa细胞暴露于IC 20的化合物，并使用Illumina转录组系统和GeneGo MetaCore软件分析处理的细胞的基因组信息。我们的研究结果表明，（IC 20 = 214.7 μM）降低了α微管蛋白基因的表达（折叠-3.7），微管中的微管蛋白（fold-3.7）和组蛋白h3（倍数=-3.03），用neovestitol治疗（IC 20 = 102.91 μM）下调前列腺素E合成酶基因（倍数=-3.12），被认为是抗癌治疗的理想靶点。这些数据为研究vestitol和neovestitol作为抗癌治疗的潜在有前途的候选药物开辟了途径。需要对本文所述结果进行毒理学、非临床和临床验证。
Vestitol and neovestitol are bioactive isoflavonoids isolated from Brazilian red propolis, a uniqueApis meliferatype of propolis botanically originated fromDalbergia ecastophyllum. Although these molecules have relevant biological effects, including anticancer and immunomodulatory activities, their mechanism(s) of action and the affected pathways remain largely unknown. Here, we carried out a pharmacogenomic analysis to investigate the effects of vestitol and neovestitol on the whole‐genome expression in human tumor cells, particularly cancer‐related target proteins. HeLa cells were exposed to the compounds at IC20and genomic information of treated cells was analyzed using the Illumina transcriptome system and GeneGo MetaCore software. Our results showed that vestitol (IC20= 214.7 μM) reduced the expression of genes enrolled with the alpha tubulin (fold −3.7), tubulin in microtubules (fold −3.7), and histone h3 (fold = −3.03), and that treatment with neovestitol (IC20= 102.91 μM) downregulated prostaglandin E synthase gene (fold = −3.12), which are considered ideal targets for anticancer therapy. These data open avenues for the study of vestitol and neovestitol as potential promising candidates for anticancer therapy. Toxicological, non‐clinical, and clinical validation of the findings presented herein is needed.