目的:根皮素是一种在某些植物中发现的天然类黄酮化合物,比如苹果和梨,以及苹果树的树皮。根皮素已被证明对细胞中的葡萄糖转运蛋白具有抑制作用,并可能抑制癌细胞的生长。然而,根皮素调节雌激素受体α(ERα)表达的机制,乳腺癌的关键转录因子,还不清楚。这项研究调查了根皮素如何影响ERα阳性人类乳腺癌细胞的生长。
方法:乳腺癌细胞系的生长,包括MCF7和T47D,使用细胞增殖和集落形成测定法检查。蛋白质印迹和半定量RT-PCR检测蛋白质和mRNA水平。分别。使用亚细胞分级分离分析细胞蛋白质的定位。瞬时转染和报道的基因测定用于阐明根皮素对细胞增殖和ERα反式激活的影响。
结果:根皮素在MCF7和T47D细胞中mRNA和蛋白水平降低ERα表达。它还抑制ERα与靶基因启动子中存在的雌激素反应元件的结合。此外,根皮素治疗抑制细胞周期蛋白D1和乳腺癌标志物基因pS2的表达,这是已知的ERα靶基因。因此,它抑制ERα阳性人乳腺癌细胞的生长。此外,发现根皮素对乳腺癌生长的抑制作用是通过ERα和ERK1/ERK2途径介导的。
结论:根皮素,从天然来源提取的二氢查尔酮,具有调节ERα功能和抑制乳腺癌细胞增殖的能力。
OBJECTIVE: Phloretin is a natural flavonoid compound found in some plants, such as apples and pears, as well as in the bark of apple trees. Phloretin has been shown to have inhibitory effects on glucose transporters in cells and can potentially inhibit the growth of cancer cells. However, the mechanism by which phloretin regulates the expression of estrogen receptor alpha (ERα), a key transcription factor in breast cancer, is still unclear. This study investigated how phloretin affects the growth of ERα positive human breast cancer cells.
METHODS: The growth of breast cancer cell lines, including MCF7 and T47D, was examined using cell proliferation and colony formation assays. Western blotting and semi-quantitative RT-PCR were used to examine protein and mRNA levels, respectively. Localization of cellular proteins was analyzed using subcellular fractionation. Transient transfection and reported gene assays were used to elucidate the impact of phloretin on cell proliferation and ERα transactivation.
RESULTS: Phloretin decreased ERα expression at the mRNA and protein levels in MCF7 and T47D cells. It also inhibited the binding of ERα to the estrogen response element present in the promoter of target genes. Moreover, treatment with phloretin inhibited the expression of cyclin D1 and breast cancer marker gene pS2, which are known ERα target genes. Consequently, it inhibited the growth of ERα-positive human breast cancer cells. Furthermore, inhibition of breast cancer growth by phloretin was found to be mediated through both the ERα and ERK1/ERK2 pathways.
CONCLUSIONS: Phloretin, a dihydrochalcone extracted from natural sources, exhibits the ability to regulate ERα function and suppress breast cancer cell proliferation.