Maxwell Thressi, Chun So-Young, Lee Kyu-Shik, Kim Soyoung, Nam Kyung-Soo
Department of Pharmacology and Intractable Disease Research Center, School of Medicine, Dongguk University, Gyeongju-si 780-350, Republic of Korea.
Int J Oncol. 2017 Feb;50(2):727-735. doi: 10.3892/ijo.2016.3825. Epub 2016 Dec 29.
Arctigenin is a plant lignan extracted from Arctium lappa that has been shown to have estrogenic properties. In spite of the health benefits of phytoestrogens reducing the risk of osteoporosis, heart disease, and menopausal symptoms, its benefits against the risk of breast cancer have not been fully elucidated. Thus, we investigated the effects of arctigenin on metastasis of breast cancer using both estrogen receptor (ER)-positive MCF-7 and ER-negative MDA-MB-231 human breast cancer cell lines to see if the effects are dependent on the status of ER expression. In ER-positive MCF-7 cells, arctigenin efficiently inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cell migration and invasion. The activity of crucial metastatic protease matrix metalloprotease (MMP)-9 in gelatin zymography was also efficiently decreased by arctigenin, as well as its mRNA expression. Notably, arctigenin exhibited similar anti-metastatic effects even in ER-negative MDA-MB-231 cells, suggesting that the anti-metastatic effects of arctigenin were not exerted via the ER. The upstream signaling pathways involved in the regulation of MMP-9 and urokinase plasminogen activator (uPA) were analyzed using western blotting. The activation of Akt, NF-κB and MAPK (ERK 1/2 and JNK 1/2) was found to be inhibited. Taken together, these data suggest that arctigenin confers anti-metastatic effects by inhibiting MMP-9 and uPA via the Akt, NF-κB and MAPK signaling pathways on breast cancer, regardless of ER expression. Therefore, we propose that the intake of arctigenin could be an effective supplement for breast cancer patients.
牛蒡子苷元是从牛蒡中提取的一种植物木脂素，已被证明具有雌激素样特性。尽管植物雌激素对降低骨质疏松症、心脏病和更年期症状的风险有益，但其对乳腺癌风险的益处尚未完全阐明。因此，我们使用雌激素受体（ER）阳性的MCF-7和ER阴性的MDA-MB-231人乳腺癌细胞系研究了牛蒡子苷元对乳腺癌转移的影响，以观察其作用是否依赖于ER表达状态。在ER阳性的MCF-7细胞中，牛蒡子苷元有效抑制了12-O-十四烷酰佛波醇-13-乙酸酯（TPA）诱导的细胞迁移和侵袭。在明胶酶谱中，关键的转移蛋白酶基质金属蛋白酶（MMP）-9的活性以及其mRNA表达也被牛蒡子苷元有效降低。值得注意的是，牛蒡子苷元在ER阴性的MDA-MB-231细胞中也表现出类似的抗转移作用，这表明牛蒡子苷元的抗转移作用不是通过ER发挥的。使用蛋白质印迹法分析了参与MMP-9和尿激酶型纤溶酶原激活剂（uPA）调节的上游信号通路。发现Akt、NF-κB和MAPK（ERK 1/2和JNK 1/2）的激活受到抑制。综上所述，这些数据表明，无论ER表达如何，牛蒡子苷元通过Akt、NF-κB和MAPK信号通路抑制MMP-9和uPA，从而赋予乳腺癌抗转移作用。因此，我们建议摄入牛蒡子苷元可能是乳腺癌患者的一种有效补充剂。
