关键词: Brazilin Breast cancer Cell invasion E-cadherin MMP-2 MMP-9 Vimentin

Mesh : Female Humans Benzopyrans / pharmacology Breast Neoplasms / pathology drug therapy metabolism genetics Cadherins / metabolism Cell Line, Tumor Epithelial-Mesenchymal Transition / drug effects Matrix Metalloproteinases / metabolism genetics MCF-7 Cells Neoplasm Invasiveness / genetics Nuclear Proteins Triple Negative Breast Neoplasms / pathology drug therapy metabolism genetics Twist-Related Protein 1 / metabolism genetics Vimentin / metabolism genetics

来  源:   DOI:10.7717/peerj.17360   PDF(Pubmed)

Abstract:
Breast cancer is the most common invasive neoplasm and the leading cause of cancer death in women worldwide. The main cause of mortality in cancer patients is invasion and metastasis, where the epithelial-mesenchymal transition (EMT) is a crucial player in these processes. Pharmacological therapy has plants as its primary source, including isoflavonoids. Brazilin is an isoflavonoid isolated from Haematoxilum brasiletto that has shown antiproliferative activity in several cancer cell lines. In this study, we evaluated the effect of Brazilin on canonical markers of EMT such as E-cadherin, vimentin, Twist, and matrix metalloproteases (MMPs). By Western blot, we evaluated E-cadherin, vimentin, and Twist expression and the subcellular localization by immunofluorescence. Using gelatin zymography, we determined the levels of secretion of MMPs. We used Transwell chambers coated with matrigel to determine the in vitro invasion of breast cancer cells treated with Brazilin. Interestingly, our results show that Brazilin increases 50% in E-cadherin expression and decreases 50% in vimentin and Twist expression, MMPs, and cell invasion in triple-negative breast cancer (TNBC) MDA-MB-231 and to a lesser extend in MCF7 ER+ breast cancer cells. Together, these findings position Brazilin as a new molecule with great potential for use as complementary or alternative treatment in breast cancer therapy in the future.
摘要:
乳腺癌是最常见的浸润性肿瘤,也是全球女性癌症死亡的主要原因。癌症患者死亡的主要原因是侵袭和转移,其中上皮-间质转化(EMT)是这些过程中的关键参与者。药物治疗以植物为主要来源,包括异黄酮。Brazilin是一种从巴西血杆菌中分离出的异黄酮,已在几种癌细胞系中显示出抗增殖活性。在这项研究中,我们评估了巴西林对EMT的典型标记如E-cadherin,波形蛋白,Twist,和基质金属蛋白酶(MMPs)。通过蛋白质印迹,我们评估了E-cadherin,波形蛋白,和Twist表达和免疫荧光的亚细胞定位。使用明胶酶谱,我们确定了MMP的分泌水平。我们使用涂有基质胶的Transwell腔室来确定用巴西林处理的乳腺癌细胞的体外侵袭。有趣的是,我们的结果表明,巴西林在E-cadherin表达增加50%,在波形蛋白和Twist表达减少50%,MMPs,三阴性乳腺癌(TNBC)MDA-MB-231和MCF7ER+乳腺癌细胞中的细胞侵袭。一起,这些发现将Brazilin定位为一种新分子,在未来的乳腺癌治疗中具有作为补充或替代治疗的巨大潜力.
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