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针对病种:乳腺癌
发表时间:2011年5月
发表国家:美国
登载刊物:肿瘤生物学和治疗
研究单位:美国约翰斯霍普金斯医科大学外科学院
研究人员:阿达茹妮 马里克等
主要结论:在IC(50) 浓度时,MA- 6,MA- 8 和MA-19 金雀异黄素衍生物可以诱导细胞凋亡, 抑制雌激素受体 α 信使 RNA 的表达并与初始化合物染料木黄酮相比增大 ER-β与ER-α水平之比.
Cancer Biology & Therapy, 2011, 11(10):883-92.
Potent genistein derivatives as inhibitors of estrogen receptor alpha-positive breast cancer
Radharani Marik, et al
Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
The estrogen receptor (ER) is a major target for the treatment of breast cancer cells. Genistein, a soy isoflavone, possesses a structure similar to estrogen and can both mimic and antagonize estrogen effects although at high concentrations it inhibits breast cancer cell proliferation. Hence, to enhance the anti-cancer activity of Genistein at lower concentrations, we have synthesized seven structurally modified derivatives of Genistein (MA-6, MA-8, MA-11, MA-19, MA-20, MA-21 and MA-22) based on the structural requirements for an optimal anti-cancer effect. Among those seven, three derivatives (MA-6, MA-8 and MA-19) showed high antiproliferative activity with IC(50) levels in the range of 1-2.5 μM, i.e., at much lower concentrations range than Genistein itself, in three ER-positive breast cancer cell lines (MCF-7, 21PT and T47D) studied. In our analysis, we noticed that at IC(50) concentrations, the MA-6, MA-8 and MA-19 Genistein derivatives induced apoptosis, inhibited ER-α messenger RNA expression and increased the ratio of ER-β to ER-α levels in a manner comparable to the parent compound Genistein. Of note, these three modified Genistein derivatives exerted their effects at concentrations 10-15 times lower than the parent compound, decreasing the likelihood of significant ER- α pathway activation, which has been a concern for Genistein. Hence these compounds might play a useful role in breast cancer chemoprevention.
美国《肿瘤生物学和治疗》,2011年5月
强效的金雀异黄素衍生物作为雌激素受体 α 阳性乳腺癌的抑制剂
阿达茹妮 马里克等
美国约翰斯霍普金斯医科大学外科学院
雌激素受体 (ER) 是治疗乳腺癌细胞的主要目标。染料木素,一种 大豆异黄酮,具有类似雌激素的结构,可以在模仿并拮抗雌激素的作用;虽然在高浓度条件下,它能抑制乳腺肿瘤细胞的增殖。因此,要提高染料木黄酮在低浓度下的抗肿瘤活性,基于最佳抗肿瘤效应的结构要求我们合成了七种结构改性的染料木黄酮衍生物(MA- 6、 MA-8、 MA-11、 MA-19、 MA-20、 MA-21 和MA-22)。在这七种之中, 三种衍生物 (MA-6、 MA-8 和MA-19)在三种 ER- 阳性乳腺癌细胞 (MCF-7、 21PT 和 T47D)中在浓度为1-2.5 μ M的IC(50) 水平范围即比染料木素本身更低的浓度范围内表现出高增殖活性。在我们的分析中,我们注意到,在IC(50) 浓度时,MA- 6,MA- 8 和MA-19 金雀异黄素衍生物可以诱导细胞凋亡, 抑制雌激素受体 α 信使 RNA 的表达并与初始化合物染料木黄酮相比增大 ER-β与ER-α水平之比。值得注意的是,这三种改性染料木黄酮衍生物在浓度比母体化合物低了 10-15 倍时仍能发挥作用,减低可能发生的ER-α 通路激活,这已经成为金雀异黄素的核心。因此这些化合物在乳房癌化学预防作用可能发挥有益的作用。石家庄霹克医药科技有限公司 400-831-3116 |