Depsidones inhibit aromatase activity and tumor cell proliferation in a co-culture of human primary breast adipose fibroblasts and T47D breast tumor cells.
Depsidones inhibit aromatase activity and tumor cell proliferation in a co-culture of human primary breast adipose fibroblasts and T47D breast tumor cells.
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DOI：
10.1016/j.toxrep.2017.03.004
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发表时间：
2017
影响因子：
--
通讯作者：
Van den Berg M
中科院分区：
文献类型：
--
作者：
Chottanapund S;Van Duursen MBM;Zwartsen A;Timtavorn S;Navasumrit P;Kittakoop P;Sureram S;Ruchirawat M;Van den Berg M
依赖性甾酮是原代人乳腺脂肪成纤维细胞中的芳香酶抑制剂。依赖性甾酮可能与乳腺癌治疗具有药物治疗相关性。乳腺肿瘤和成纤维细胞的共培养物为雌激素依赖性乳腺癌创建了体内真实的体外模型。已知来自海洋真菌Aspergillus unguis的天然存在的缩酚酮具有显著的抗癌活性，但它们的作用机制仍然难以捉摸。本研究的目的是检查两种常见的depretinone，unguinol和aspergillusidone A，在人原代乳腺脂肪成纤维细胞和激素反应性T47D乳腺肿瘤细胞的共培养系统中的抗芳香化酶活性。使用该体外模型，显示这些Dependanone抑制T47D肿瘤细胞的生长最可能是通过抑制芳香酶（CYP 19）活性。将这些地匹西酮的IC 50值与芳香酶抑制剂来曲唑和依西美坦进行比较。来曲唑和阿司美坦的IC 50值分别为0.19和0.14 μM，而乌桂醇和阿司琼酮A的IC 50值分别为9.7和7.3 μM。我们的研究结果表明，在depressone可能有芳香化酶抑制剂与可能的药物治疗相关。
Depsidones are aromatase inhibitors in primary human breast adipose fibroblasts. Depsidones may have pharmacotherapeutical relevance for breast cancer treatment. Co-cultures of breast tumor and fibroblasts cells create a vivo realistic in vitro model for estrogen dependent breast cancer. Naturally occurring depsidones from the marine fungus Aspergillus unguis are known to have substantial anti-cancer activity, but their mechanism of action remains elusive. The purpose of this study was to examine the anti-aromatase activity of two common depsidones, unguinol and aspergillusidone A, in a co-culture system of human primary breast adipose fibroblasts and hormonal responsive T47D breast tumor cells. Using this in vitro model it was shown that these depsidones inhibit the growth of T47D tumor cells most likely via inhibition of aromatase (CYP19) activity. The IC50 values of these depisidones were compared with the aromatase inhibitors letrozole and exemestane. Letrozole and exemestane had IC50 values of respectively, 0.19 and 0.14 μM, while those for Unguinol and Aspergillusidone A were respectively, 9.7 and 7.3 μM. Our results indicate that among the depsidones there maybe aromatase inhibitors with possible pharmacotherapeutical relevance.