Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran.
Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
Phytother Res. 2021 Apr;35(4):1967-1982. doi: 10.1002/ptr.6940. Epub 2020 Nov 20.
Breast cancer is the leading cause of cancer death in women worldwide. Due to the side effects of current chemo-reagents on healthy tissues, it is essential to search for alternative compounds with less toxicity and better efficacy. In the present study, we have investigated the anticancer effects of flavonoid xanthomicrol on the mice breast cancer model using MTT assay, cell cycle and Annexin/PI analysis, colony formation assay, H&E staining, immunohistochemistry, and miRNA analysis. Our results demonstrated that xanthomicrol decreased the cell viability and clonogenic capability, induced G1-arrest and apoptosis in the breast cancer cells in vitro, and caused a significant reduction in the volume and weight of mice tumors in vivo. In addition, xanthomicrol reduced the expression of TNFα, VEGF, MMP9, and Ki67, while upregulating the expression of apoptotic markers such as Bax, caspase3, and caspase9. Finally, the expression of miR21, miR27, and miR125, known as oncomirs, decreased significantly after xanthomicrol administration, while the expression of miR29 and miR34, functioning as tumor suppressors, increased significantly (p < .001). Our data demonstrated that xanthomicrol can induce apoptosis and suppress angiogenesis in breast cancer cells due to its inhibitory effect on oncomirs and its stimulatory effect on tumor suppressor miRNAs.
乳腺癌是全球女性癌症死亡的主要原因。由于当前化疗试剂对健康组织的副作用，寻找毒性更小、疗效更好的替代化合物至关重要。在本研究中，我们使用 MTT 检测、细胞周期和 Annexin/PI 分析、集落形成检测、H&E 染色、免疫组织化学和 miRNA 分析，研究了黄酮类化合物黄烷醇对乳腺癌小鼠模型的抗癌作用。我们的结果表明，黄烷醇在体外降低了乳腺癌细胞的活力和克隆形成能力，诱导了 G1 期阻滞和细胞凋亡，并导致体内小鼠肿瘤体积和重量的显著减少。此外，黄烷醇降低了 TNFα、VEGF、MMP9 和 Ki67 的表达，同时上调了促凋亡标志物如 Bax、caspase3 和 caspase9 的表达。最后，已知作为致癌 miRNA 的 miR21、miR27 和 miR125 的表达在黄烷醇给药后显著降低，而作为肿瘤抑制 miRNA 的 miR29 和 miR34 的表达显著增加（p<0.001）。我们的数据表明，黄烷醇可以通过抑制致癌 miRNA 和刺激肿瘤抑制 miRNA 来诱导乳腺癌细胞凋亡和抑制血管生成。
