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9-Hydroxycanthin-6-one isolated from stem bark of Ailanthus altissima induces ovarian cancer cell apoptosis and inhibits the activation of tumor-associated macrophages
Chemico-Biological Interactions ( IF 4.7 ) Pub Date : 2017-12-07 , DOI: 10.1016/j.cbi.2017.12.011
Miran Jeong , Hye Mi Kim , Ji-Hye Ahn , Kyung-Tae Lee , Dae Sik Jang , Jung-Hye Choi

The stem bark of Ailanthus altissima is used in traditional medicine in Asia to treat a variety of diseases, including cancer. The aim of this study was to identify compounds with tumoricidal activity from A. altissima stem bark and to investigate their mechanisms of action. Among the 13 compounds isolated from the ethyl acetate fraction of A. altissima stem bark, the β-carboline alkaloid 9-hydroxycanthin-6-one had potent cytotoxicity in all three ovarian cancer cell types examined. 9-Hydroxycanthin-6-one induced apoptosis through the activation of caspases-3, -8, and -9. 9-Hydroxycanthin-6-one increased the intracellular levels of reactive oxygen species (ROS), and pre-treatment with the antioxidant N-acetyl-l-cysteine (NAC) attenuated the pro-apoptotic activity of 9-hydroxycanthin-6-one. Additionally, 9-hydroxycanthin-6-one was found to decrease the expressions of MCP-1 and RANTES, major determinants of macrophage recruitment at tumor sites, in ovarian cancer cells. Treatment with 9-hydroxycanthin-6-one inhibited the levels of M2 phenotype markers and some cancer-promoting factors, such as MMP-2, MMP-9, and VEGF, in macrophages educated in ovarian cancer conditioned medium. Taken together, these data suggest that 9-hydroxycanthin-6-one isolated from A. altissima stem bark induces apoptosis in human ovarian cancer cells through the caspase- and ROS-dependent pathways and inhibits the activation of tumor-associated macrophages.



中文翻译:

臭椿的茎皮中分离得到的9-Hydroxycanthin- 6-1诱导卵巢癌细胞凋亡并抑制肿瘤相关巨噬细胞的活化

臭椿(Ailanthus altissima)的茎皮被用于亚洲的传统医学中,以治疗包括癌症在内的多种疾病。这项研究的目的是从A. altissima茎皮中鉴定具有杀伤活性的化合物,并研究其作用机理。从拟南芥茎皮的乙酸乙酯级分中分离出的13种化合物中,β-咔啉生物碱9-羟基canthin-6-one在所研究的所有三种卵巢癌细胞类型中均具有强大的细胞毒性。9-Hydroxycanthin-6-one通过激活caspases-3,-8和-9诱导细胞凋亡。9-Hydroxycanthin-6-one增加了细胞内活性氧(ROS)的水平,并用抗氧化剂N-乙酰基-l进行了预处理-半胱氨酸(NAC)减弱了9-羟基canthin-6-one的促凋亡活性。另外,发现9-羟基canthin-6-一降低卵巢癌细胞中MCP-1和RANTES的表达,MC​​P-1和RANTES是巨噬细胞在肿瘤部位募集的主要决定因素。在卵巢癌条件培养基中培养的巨噬细胞中,用9-hydroxycanthin-6-one处理可抑制M2表型标记物和某些促癌因子(如MMP-2,MMP-9和VEGF)的水平。综上所述,这些数据表明,从拟南芥茎皮中分离出的9-羟基canthin-6-可通过caspase和ROS依赖性途径诱导人卵巢癌细胞凋亡,并抑制肿瘤相关巨噬细胞的活化。

更新日期:2017-12-07
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