Department of Biological Sciences, Vittal Mallya Scientific Research Foundation, BTM II Stage, Bangalore 560076, India.
Chemistry Division, Vittal Mallya Scientific Research Foundation, BTM II Stage, Bangalore 560076, India.
Bioorg Chem. 2014 Oct;56:54-61. doi: 10.1016/j.bioorg.2014.06.004. Epub 2014 Jun 26.
Abyssinones I and II are prenylated flavanones existing in plant Erythrina abyssinica showing diverse biological activities including anticancer activities. We synthesized racemic mixtures of these flavanones from corresponding chalcones and herein we report for the first time the molecular mechanisms of cell death, anti-proliferative effect and ability to induce apoptosis in human cervical carcinoma (HeLa) cells. Cytotoxicity was assessed by MTT assay to determine LD50 for prenylated chalcones and their corresponding flavones. Abyssinones promoted apoptosis by up regulation of p53 and Bax, along with down regulation of Bcl-2. Apoptosis induction was mediated through mitochondrial pathway releasing cytochrome c and Apaf-1 into cytosol; associated with activation of caspase-3. Further they were able to decrease the expression of cell proliferation markers PCNA and cyclin D1 indicating anti proliferative activity. These observations demonstrate that abyssinones trigger apoptosis via mitochondrial pathway by activation of caspase-3 and disrupts cell cycle.
阿比西尼亚酮 I 和 II 是存在于植物安哥拉山黧豆中的一种苯丙素类黄酮，具有多种生物活性，包括抗癌活性。我们从相应的查尔酮合成了这些类黄酮的外消旋混合物，本文首次报道了它们诱导人宫颈癌（HeLa）细胞死亡、抗增殖作用和诱导细胞凋亡的分子机制。通过 MTT 测定法评估细胞毒性，以确定prenylated chalcones 和它们相应的黄酮的 LD50。阿比西尼亚酮通过上调 p53 和 Bax，同时下调 Bcl-2 来促进细胞凋亡。凋亡诱导是通过线粒体途径介导的，将细胞色素 c 和 Apaf-1 释放到细胞质中；与 caspase-3 的激活有关。此外，它们还能够降低细胞增殖标志物 PCNA 和 cyclin D1 的表达，表明具有抗增殖活性。这些观察结果表明，阿比西尼亚酮通过激活 caspase-3 经由线粒体途径触发细胞凋亡，并破坏细胞周期。
