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Cytotoxicity, anti-angiogenic, apoptotic effects and transcript profiling of a naturally occurring naphthyl butenone, guieranone A

机译：天然存在的萘基丁烯酮，圭那酮A的细胞毒性，抗血管生成，凋亡作用和转录谱分析

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Background Malignant diseases are responsible of approximately 13% of all deaths each year in the world. Natural products represent a valuable source for the development of novel anticancer drugs. The present study was aimed at evaluating the cytotoxicity of a naphtyl butanone isolated from the leaves of Guiera senegalensis, guieranone A (GA). Results The results indicated that GA was active on 91.67% of the 12 tested cancer cell lines, the IC50 values below 4 μg/ml being recorded on 83.33% of them. In addition, the IC50 values obtained on human lymphoblastic leukemia CCRF-CEM (0.73 μg/ml) and its resistant subline CEM/ADR5000 (1.01 μg/ml) and on lung adenocarcinoma A549 (0.72 μg/ml) cell lines were closer or lower than that of doxorubicin. Interestingly, low cytotoxicity to normal hepatocyte, AML12 cell line was observed. GA showed anti-angiogenic activity with up to 51.9% inhibition of the growth of blood capillaries on the chorioallantoic membrane of quail embryo. Its also induced apotosis and cell cycle arrest. Ingenuity Pathway Analysis identified several pathways in CCRF-CEM cells and functional group of genes regulated upon GA treatment (P ), the Cell Cycle: G2/M DNA Damage Checkpoint Regulation and ATM Signaling pathways being amongst the four most involved functional groups. Conclusion The overall results of this work provide evidence of the cytotoxic potential of GA and supportive data for its possible use in cancer chemotherapy.
机译：背景世界每年，恶性疾病约占所有死亡人数的13％。天然产物是开发新型抗癌药物的宝贵资源。本研究旨在评估从塞内加尔圭亚那（Guiera senegalensis）的叶子中分离出的萘基丁酮（guieranone A）的细胞毒性。结果结果表明，GA对12种测试的癌细胞系有活性，其中IC 50 值低于4μg/ ml的记录有83.33％。此外，对人淋巴细胞白血病CCRF-CEM（0.73μg/ ml）及其耐药亚系CEM / ADR5000（1.01μg/ ml）和对肺腺癌A549（0.72μg/ ml）的IC 50 值ml）细胞系比阿霉素更接近或更低。有趣的是，观察到对正常肝细胞AML12细胞系的低细胞毒性。 GA显示出抗血管生成活性，对鹌鹑胚胎绒毛膜上的毛细血管生长的抑制作用高达51.9％。它还诱导细胞凋亡和细胞周期停滞。独创性途径分析确定了CCRF-CEM细胞和基因功能组中受GA处理（P）调控的几种途径，其中细胞周期：G2 / M DNA损伤检查点调节和ATM信号传导途径是四个参与程度最高的功能组。结论这项工作的总体结果为GA的细胞毒性潜力提供了证据，并为GA可能用于癌症化疗提供了支持性数据。

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