Title

Novel Sulfonanilide Analogues Suppress Aromatase Expression and Activity in Breast Cancer Cells Independent of COX-2 Inhibition

Document Type

Article

Publication Date

2-1-2006

Publication Title

Journal of Medicinal Chemistry

Abstract

Aromatase is a particularly attractive target in the treatment of estrogen receptor positive breast cancer. Aromatase levels in breast cancer cells are enhanced by prostaglandins and reduced by COX inhibitors. The synthesis and biological evaluation of a novel series of sulfonanilide analogues derived from the COX-2 selective inhibitor NS-398 are described. The compounds suppress aromatase enzyme activity in SK-BR-3 breast cancer cells in a dose- and time-dependent manner. The effect of these compounds on COX-2 inhibition is investigated in breast cancer cells as well. Structure−activity analysis does not find a correlation between aromatase suppression and COX-2 inhibition. Microsomal aromatase inhibition studies rule out the possibility of direct enzyme inhibition. Real-time PCR analysis demonstrates that the sulfonanilide analogues decrease aromatase gene transcription in SK-BR-3 cells. These studies suggest that the novel sulfonanilide compounds suppress aromatase activity and transcription in SK-BR-3 breast cancer cells independent of COX-2 inhibition.

Comments

This work was supported by the National Institutes of Health (NIH) Grant R01 CA73698 (R.W.B.), the NIH Chemistry and Biology Interface Training Program Grant T32 GM08512 (E.S.D.-C.), and The Ohio State University Comprehensive Cancer Center Breast Cancer Research Fund.

DOI

10.1021/jm051126f

Volume

49

Issue

4