Pachón-Peña Gisela, Reyes-Zurita Fernando J, Deffieux Gerard, Azqueta Amaia, de Cerain Adela López, Centelles Josep J, Creppy Edmond E, Cascante Marta
Department of Biochemistry and Molecular Biology, Institute of Biomedicine of the University of Barcelona (IBUB) and Unit Associated with CSIC, Diagonal 645, Barcelona, Spain.
Toxicology. 2009 Oct 29;264(3):192-7. doi: 10.1016/j.tox.2009.08.009. Epub 2009 Aug 15.
Several studies have been performed reporting antitumoral activity of different mushroom extracts. The current study reports the antiproliferative activity of flavomannin-6,6'-dimethylether obtained from a very common edible mushroom: Tricholoma equestre(L.)P.Kumm, and the characterization of its effects at molecular level. Concentrations causing 50% and 80% growth inhibition on human adenocarcinoma colorectal Caco-2 cells were determined (in microg/mL: IC(50)=96+/-3 after 24 h and 78+/-7 after 48 h, IC(80)=112+/-4 after 24 h and 90+/-3 after 48 h) by using MTT method. It was demonstrated that flavomannin-6,6'-dimethylether induced an arrest in G0/G1 phase of the cell cycle by flow cytometry analysis and an increase of p27 protein level by Western blot. Furthermore, this compound did not induce apoptosis by flow cytometry or DNA fragmentation by gel electrophoresis. Thus, it could be a promising agent due to its cytostatic effect against Caco-2 tumoral cells, and the absence of a genotoxic effect.
已经开展了多项研究报告不同蘑菇提取物的抗肿瘤活性。本研究报告了从一种非常常见的可食用蘑菇——黄绿口蘑(Tricholoma equestre (L.) P.Kumm)中获得的黄酮甘露聚糖-6,6'-二甲醚的抗增殖活性,以及其在分子水平上作用的特征。通过MTT法测定了对人结肠腺癌Caco-2细胞产生50%和80%生长抑制的浓度(以微克/毫升计:24小时后IC(50)=96±3,48小时后IC(50)=78±7;24小时后IC(80)=112±4,48小时后IC(80)=90±3)。通过流式细胞术分析表明,黄酮甘露聚糖-6,6'-二甲醚诱导细胞周期在G0/G1期停滞,通过蛋白质免疫印迹法表明其使p27蛋白水平升高。此外,该化合物通过流式细胞术未诱导细胞凋亡,通过凝胶电泳未诱导DNA片段化。因此,由于其对Caco-2肿瘤细胞的细胞抑制作用以及不存在遗传毒性作用,它可能是一种有前景的药物。