Depsidones inhibit aromatase activity and tumor cell proliferation in a co-culture of human primary breast adipose fibroblasts and T47D breast tumor cells

- 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.

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