Department of Biochemistry, Faculty of science, University of Dschang, Dschang, Cameroon.
Cell Div. 2012 Jun 20;7(1):16. doi: 10.1186/1747-1028-7-16.
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).
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 < 0.05), the Cell Cycle: G2/M DNA Damage Checkpoint Regulation and ATM Signaling pathways being amongst the four most involved functional groups.
The overall results of this work provide evidence of the cytotoxic potential of GA and supportive data for its possible use in cancer chemotherapy.
恶性疾病约占全球每年死亡人数的 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 Guiera senegalensis 叶中分离得到的萘基丁酮（guieranone A，GA）的细胞毒性。
结果表明，GA 对 12 种测试的癌细胞系中的 91.67%具有活性，其中 83.33%的 IC50 值低于 4 μg/ml。此外，GA 在人淋巴母细胞白血病 CCRF-CEM（0.73 μg/ml）及其耐药亚系 CEM/ADR5000（1.01 μg/ml）和肺腺癌细胞 A549（0.72 μg/ml）中的 IC50 值更接近或低于阿霉素。有趣的是，GA 对正常肝细胞 AML12 系的细胞毒性较低。GA 具有抗血管生成活性，可抑制鹌鹑胚胎绒毛尿囊膜上的毛细血管生长达 51.9%。它还诱导细胞凋亡和细胞周期停滞。通路分析鉴定了 CCRF-CEM 细胞中的几个通路和 GA 处理后受调控的基因功能组（P<0.05），其中细胞周期：G2/M DNA 损伤检查点调控和 ATM 信号通路是四个最相关的功能组之一。
这项工作的总体结果提供了 GA 细胞毒性潜力的证据，并为其在癌症化疗中的可能应用提供了支持性数据。
