Park Sin-Aye, Kim Eun-Hee, Na Hye-Kyung, Surh Young-Joon
College of Pharmacy, Seoul National University, Shillim-dong, Kwanak-gu, Seoul 151-742, Korea.
Ann N Y Acad Sci. 2007 Jan;1095:545-53. doi: 10.1196/annals.1397.059.
Ginsenosides, ingredients of ginseng, have a wide array of pharmacologic effects. Especially, ginsenosides Rk1, Rg3, and Rg5 derived from heat-processed ginseng have been shown to possess substantial anti-tumor-promoting effects. KG-135 is a formulated complex that contains several antitumorigenic ginsenosides, such as Rk1, Rg3, Rg5, Rk2, Rk3, Rs3, Rs4, Rs5, Rs6, Rs7, etc. The present article was aimed at evaluating the chemopreventive as well as anti-inflammatory effects of KG-135 in the human breast epithelial cell line (MCF-10A). One of the well-recognized molecular targets for chemoprevention is cyclooxygenase-2 (COX-2) that is abnormally upregulated in many premalignant and malignant tissues and cells. In this study, we found that KG-135 inhibited COX-2 expression in MCF-10A cells stimulated with a prototype tumor promotor 12-O-tetradecanoylphorbol-13-acetate (TPA). Since the transcription factor activator protein-1 (AP-1) plays a role in tumor promotion and is also known to regulate COX-2 induction, we attempted to determine the effect of KG-135 on TPA-induced activation of AP-1. Cotreatment with KG-135 resulted in a decrease in TPA-induced DNA binding of AP-1. In addition, KG-135 inhibited TPA-induced phosphorylation of c-Jun N-terminal kinases (JNK) that regulates COX-2 expression in MCF-10A cells. The JNK inhibitor SP600125 attenuated COX-2 expression in TPA-treated MCF-10A cells. Taken together, the above findings suggest that KG-135 inhibits TPA-induced COX-2 expression in MCF-10A cells by blocking the JNK/AP-1 signaling pathway.
人参皂苷是人参的成分，具有广泛的药理作用。特别是，经热处理的人参衍生的人参皂苷Rk1、Rg3和Rg5已被证明具有显著的抗肿瘤促进作用。KG-135是一种配方复合物，含有多种抗肿瘤人参皂苷，如Rk1、Rg3、Rg5、Rk2、Rk3、Rs3、Rs4、Rs5、Rs6、Rs7等。本文旨在评估KG-135在人乳腺上皮细胞系（MCF-10A）中的化学预防和抗炎作用。化学预防的一个公认分子靶点是环氧合酶-2（COX-2），它在许多癌前和恶性组织及细胞中异常上调。在本研究中，我们发现KG-135抑制了用原型肿瘤促进剂12-O-十四酰佛波醇-13-乙酸酯（TPA）刺激的MCF-10A细胞中COX-2的表达。由于转录因子激活蛋白-1（AP-1）在肿瘤促进中起作用，并且已知也调节COX-2的诱导，我们试图确定KG-135对TPA诱导的AP-1激活的影响。与KG-135共同处理导致TPA诱导的AP-1 DNA结合减少。此外，KG-135抑制了TPA诱导的c-Jun N端激酶（JNK）的磷酸化，JNK调节MCF-10A细胞中COX-2的表达。JNK抑制剂SP600125减弱了TPA处理的MCF-10A细胞中COX-2的表达。综上所述，上述发现表明KG-135通过阻断JNK/AP-1信号通路抑制TPA诱导的MCF-10A细胞中COX-2的表达。
