Document Type

Article

Publication Date

10-1-2010

Publication Title

The Journal of Steroid Biochemistry and Molecular Biology

Abstract

Cyclooxygenase-2 (COX-2) inhibitor nimesulide derivatives compounds A and B decreased aromatase activity in breast cancer cells via a novel mechanism different to aromatase inhibitors (AIs), and were defined as “aromatase suppressors”. Breast carcinoma cells (MCF-7aro and T47Daro) transfected with aromatase full gene were used to explore the mechanisms of the two compounds. They dose and time-dependently suppressed aromatase activity in MCF-7aro and T47Daro cells in the nanomole range. However, they neither directly inhibited aromatase, nor improved aromatase degradation even at much higher concentrations. They could also suppress androgen stimulated cell growth, but did not affect estrogen enhanced cell proliferation. These results suggest that compounds A and B selectively interfere with aromatase in breast cancer cells, but not estrogen receptor (ER) downstream to disrupt androgen mediated cell growth. Interestingly, compound B effectively inhibited LTED (long-term estrogen deprived MCF-7aro cell) cell growth, which is a model for AIs resistance, with an IC50 of 4.68 ± 0.54 μM. The results indicate that compound B could potentially overcome AI resistance in breast cancer cell and could be used as a lead to design more potent derivatives.

Comments

This work was supported by grants from the National Institutes of Health CA44735 (SC), ES08528 (SC), and a startup fund from CSU (BSu).

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

DOI

10.1016/j.jsbmb.2010.06.004

Version

Postprint

Volume

122

Issue

4

Included in

Chemistry Commons

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