Department of Health Education and Administration, Jinhua Municipal Central Hospital, Jinhua, 321000, China.
Department of Clinical Nutrition, Jinhua Municipal Central Hospital, Jinhua, 321000, China.
Toxicol Lett. 2019 Sep 15;312:65-71. doi: 10.1016/j.toxlet.2019.04.030. Epub 2019 Apr 29.
Shikimic acid (SA), a widely-known hydroaromatic compound enriched in Bracken fern and Illicium verum (also known as Chinese star anise), increases the risk of gastric and esophageal carcinoma, nevertheless, the influence of SA on breast cancer remains indistinct. Herein we found that, with models in vitro, SA significantly promoted estrogen receptor(ER) positive cells proliferation and NF-κB activation was involved in it. Moreover, our data showed that IκBα, a critically endogenous inhibitor of NF-κB, was repressed. Subsequently, we found increase of miR-300 by SA treatment sand miR-300 could target IκBα mRNA. Additionally, inhibition of miR-300 abrogated the repression of IκBα by SA. As a result, miR-300 was also involved in NF-κB activation and breast cancer cells proliferation promotion due to SA exposure. Taken together, with ER-positive breast cancer cell models in vitro, MCF-7 and T47D, our results implied that SA promoted breast cancer cells proliferation via a miR-300-induced NF-κB dependent pathway controlling cell cycle proteins.
莽草酸(SA)是一种广泛存在于蕨类植物和八角茴香(也称为中国八角茴香)中的 Hydroaromatic 化合物,它会增加胃癌和食管癌的风险,然而,SA 对乳腺癌的影响尚不清楚。在这里,我们发现,在体外模型中,SA 显著促进了雌激素受体(ER)阳性细胞的增殖,其中涉及 NF-κB 的激活。此外,我们的数据表明,SA 处理后 IκBα(NF-κB 的关键内源性抑制剂)受到抑制。随后,我们发现 SA 处理可增加 miR-300 的表达,而 miR-300 可靶向 IκBα mRNA。此外,抑制 miR-300 可消除 SA 对 IκBα 的抑制作用。因此,由于暴露于 SA,miR-300 也参与了 NF-κB 的激活和乳腺癌细胞增殖的促进。总之,在体外 ER 阳性乳腺癌细胞模型 MCF-7 和 T47D 中,我们的结果表明,SA 通过 miR-300 诱导的 NF-κB 依赖性途径促进乳腺癌细胞增殖,该途径控制细胞周期蛋白。