Marine Biomedical and Biotechnology Research, Harbor Branch Oceanographic Institute, Florida Atlantic University, 5600 US 1 North, Ft. Pierce, FL 34946, USA.
Mar Drugs. 2021 Apr 28;19(5):249. doi: 10.3390/md19050249.
Cancer cells grown in spheroid conditions interact with each other and the extracellular matrix, providing a better representation of the in vivo environment than two-dimensional cultures and are a more clinically relevant model. A discrete screening of genetically diverse marine samples in the spheroid assay led to the identification of a novel activity for the known compound furospinulosin 1. This compound shows activity against MDA-MB-231 triple negative breast cancer cells grown as spheroids and treated for 24 or 48 h. No cytotoxicity was seen in traditional two-dimensional adherent cultures treated for a longer time (72 h). A reverse phase protein array (RPPA) confirmed the limited activity of the compound in cells grown traditionally and revealed changes in protein expression when cells are grown as spheroids that are associated with better clinical prognosis. Analysis of the RPPA data through the Broad institute's connectivity map suggested the hypothesis that furospinulosin 1 functions as an MEK inhibitor. Analysis of the RPPA data through STRING supports the apoptosis observed. The selectivity exhibited by furospinulosin 1 for triple negative breast cancer cells only when grown as spheroids makes it an interesting compound with strong therapeutic potential that merits further study.
在球体条件下生长的癌细胞相互作用并与细胞外基质相互作用，提供了比二维培养更好的体内环境代表性，并且是更具临床相关性的模型。在球体测定中对遗传多样化的海洋样本进行离散筛选，导致鉴定出已知化合物呋喃螺旋素 1 的新活性。该化合物对作为球体生长并在 24 或 48 小时内处理的 MDA-MB-231 三阴性乳腺癌细胞具有活性。在传统的二维贴壁培养中，用更长时间（72 小时）处理时没有观察到细胞毒性。反向蛋白质阵列（RPPA）证实了该化合物在传统培养细胞中的有限活性，并揭示了当细胞作为球体生长时与更好的临床预后相关的蛋白表达变化。通过 Broad 研究所的连接图谱对 RPPA 数据进行分析表明，呋喃螺旋素 1 作为 MEK 抑制剂发挥作用的假设。通过 STRING 对 RPPA 数据进行分析支持观察到的细胞凋亡。呋喃螺旋素 1 仅在作为球体生长的三阴性乳腺癌细胞中表现出的选择性，使其成为一种具有强烈治疗潜力的有趣化合物，值得进一步研究。
