Chottanapund Suthat, Van Duursen M B M, Zwartsen Anne, Timtavorn Supatchaya, Navasumrit Panida, Kittakoop Prasat, Sureram Sanya, Ruchirawat Mathuros, Van den Berg Martin
Chulabhorn Graduate Institute, Kamphaeng Phet 6 Road, Laksi, Bangkok 10210, Thailand.
Chulabhorn Research Institute, Kamphaeng Phet 6 Road, Laksi, Bangkok 10210, Thailand.
Toxicol Rep. 2017 Mar 19;4:165-171. doi: 10.1016/j.toxrep.2017.03.004. eCollection 2017.
Naturally occurring depsidones from the marine fungus 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 model it was shown that these depsidones inhibit the growth of T47D tumor cells most likely via inhibition of aromatase (CYP19) activity. The IC values of these depisidones were compared with the aromatase inhibitors letrozole and exemestane. Letrozole and exemestane had IC 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.
已知从海洋真菌中天然产生的缩酚酸环醚具有显著的抗癌活性，但其作用机制仍不清楚。本研究的目的是在人原发性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，检测两种常见缩酚酸环醚——耳壳藻酚和曲霉缩酚酸环醚A的抗芳香化酶活性。使用该模型表明，这些缩酚酸环醚最有可能通过抑制芳香化酶（CYP19）活性来抑制T47D肿瘤细胞的生长。将这些缩酚酸环醚的IC值与芳香化酶抑制剂来曲唑和依西美坦进行比较。来曲唑和依西美坦的IC值分别为0.19和0.14 μM，而耳壳藻酚和曲霉缩酚酸环醚A的IC值分别为9.7和7.3 μM。我们的结果表明，在缩酚酸环醚中可能存在具有潜在药物治疗意义的芳香化酶抑制剂。
