克隆形成试验
磺酰罗丹明B细胞培养试剂染料
三阴性乳腺癌
细胞毒性
人口
癌症干细胞
细胞毒性T细胞
癌症研究
膜联蛋白
流式细胞术
生长抑制
癌细胞
细胞凋亡
生物
化学
分子生物学
癌症
干细胞
乳腺癌
体外
医学
生物化学
细胞生物学
遗传学
环境卫生
作者
Aline Brito de Lima,Camila de Souza Barbosa,Alessandra Mirtes Marques Neves Gonçalves,Fábio Vieira dos Santos,Gustavo Henrique Ribeiro Viana,Fernando de Pilla Varotti,Luciana Maria Silva
摘要
Abstract Triple‐negative breast cancer ( TNBC ) is one of the most aggressive cancers in women. Additionally, presence of residual cancer stem cells ( CSC ) in TNBC has challenged the efficacy of chemotherapy. Thus, the development of new molecules with potential action against CSC is fundamental. In this study, six synthetic analogues of theonelladin C, a 3‐alkylpyridine marine alkaloid, were tested for cytotoxic activity against human TNBC cell line ( BT ‐549) and tumorspheres derived from BT ‐549. Cytotoxicity assay was performed by sulforhodamine B ( SRB ). BT ‐549 and tumorspheres were examined for CD 44 +/high / CD 24 −/low markers, indicative of CSC profile, by flow cytometry. Clonogenic assay was performed to verify inhibiting growth of tumorspheres by the synthetic analogues. Cell death by apoptosis was investigated employing annexin V assay. SRB assay on BT ‐549 cells revealed that compounds 1c and 2c were the most active of the series, with IC 50 values of 18.66 and 9.8 μ m , respectively. Compounds 1c and 2c were able to reduce both CSC ‐like population ( CD 44 +/high / CD 24 −/low ) and non‐ CSC population ( CD 44 +/high / CD 24 +/high ) in tumorsphere model. Clonogenic and annexin V assays confirmed the ability of 1c and 2c to induce growth inhibition and apoptosis in BT ‐549 cells and tumorspheres. These preliminary data indicate that these compounds are a promising class for development of anticancer agents.
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