Park Jong-Shik, Bang Ok-Sun, Kim Jinhee
KM-Based Herbal Drug Development Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon, Korea.
Integr Med Res. 2014 Jun;3(2):67-73. doi: 10.1016/j.imr.2013.10.004. Epub 2013 Oct 11.
The transcription factor signal transducer and activator of transcription 3 (Stat3) is constitutively activated in many human cancers. It promotes tumor cell proliferation, inhibits apoptosis, induces angiogenesis and metastasis, and suppresses antitumor host immune responses. Therefore, Stat3 has emerged as a promising molecular target for cancer therapies. In this study, we evaluated the Stat3-suppressive activity of 38 herbal medicines traditionally used in Korea.
Medicinal herb extracts in 70% ethanol were screened for their ability to suppress Stat3 in the A549 human lung cancer cell line. A Stat3-responsive reporter assay system was used to detect intracellular Stat3 activity in extract-treated cells, and Western blot analyses were performed to measure the expression profiles of Stat3-regulated proteins.
Fifty percent of the 38 extracts possessed at least mild Stat3-suppressive activities (i.e., activity less than 75% of the vehicle control). Ethanol extracts of L., Weber, L., Hance, Sieb., Thunb., and (Lour.) Baill inhibited up to 75% of the vehicle control Stat3 activity level. A549 cells treated with these extracts also had reduced Bcl-xL, Survivin, c-Myc, and Mcl-1 expression.
Many medicinal herbs traditionally used in Korea contain Stat3 activity-suppressing substances. Because of the therapeutic impact of Stat3 inhibition, these results could be useful when developing novel cancer therapeutics from medicinal herbs.
转录因子信号转导与转录激活因子3(Stat3)在许多人类癌症中持续激活。它促进肿瘤细胞增殖,抑制细胞凋亡,诱导血管生成和转移,并抑制抗肿瘤宿主免疫反应。因此,Stat3已成为癌症治疗中一个有前景的分子靶点。在本研究中,我们评估了韩国传统使用的38种草药对Stat3的抑制活性。
筛选70%乙醇中的草药提取物对A549人肺癌细胞系中Stat3的抑制能力。使用Stat3反应性报告基因检测系统检测提取物处理细胞中的细胞内Stat3活性,并进行蛋白质印迹分析以测量Stat3调节蛋白的表达谱。
38种提取物中有50%至少具有轻度的Stat3抑制活性(即活性低于溶剂对照的75%)。地黄、韦伯地黄、朝鲜地黄、汉地黄、紫背地黄、地黄和巴伊地黄的乙醇提取物抑制了高达75%的溶剂对照Stat3活性水平。用这些提取物处理的A549细胞中Bcl-xL、Survivin、c-Myc和Mcl-1的表达也降低。
韩国传统使用的许多草药含有抑制Stat3活性的物质。由于抑制Stat3具有治疗作用,这些结果在从草药开发新型癌症治疗药物时可能有用。