Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung 402, Taiwan, Republic of China.
J Nat Prod. 2012 Apr 27;75(4):630-5. doi: 10.1021/np200866z. Epub 2012 Feb 23.
Breast cancer cells express ABCG2 transporters, which mediate multidrug resistance. Discovering a novel compound that can suppress ABCG2 expression and restore drug sensitivity could be the key to improving breast cancer therapeutics. In the current work, one new nor-neolignan, asperjinone (1), as well as 12 other known compounds, was isolated from Aspergillus terreus. The structure of the new isolate was determined by spectroscopic methods. Among these isolates, terrein (2) displayed strong cytotoxicity against breast cancer MCF-7 cells. Treatment with terrein (2) significantly suppressed growth of ABCG2-expressing breast cancer cells. This suppressive effect was achieved by inducing apoptosis via activating the caspase-7 pathway and inhibiting the Akt signaling pathway, which led to a decrease in ABCG2-expressing cells and a reduction in the side-population phenotype.
乳腺癌细胞表达 ABCG2 转运蛋白，介导多药耐药。发现一种能够抑制 ABCG2 表达并恢复药物敏感性的新型化合物可能是改善乳腺癌治疗的关键。在本研究中，从土曲霉中分离到一种新的去甲新木脂素asperjinone（1）和 12 种其他已知化合物。通过光谱方法确定了新分离物的结构。在这些分离物中，terrein（2）对乳腺癌 MCF-7 细胞显示出很强的细胞毒性。terrein（2）处理显著抑制 ABCG2 表达的乳腺癌细胞的生长。这种抑制作用是通过激活半胱天冬酶-7 途径和抑制 Akt 信号通路诱导细胞凋亡来实现的，这导致 ABCG2 表达细胞减少和侧群表型减少。
