jcc-76 and Breast-Neoplasms

Compound JCC76 selectively inhibited the proliferation of human epidermal growth factor 2 (Her2) over-expressed breast cancer cells. In the current study, a ligand based structural optimization was performed to generate new analogs, and we identified derivatives 16 and 17 that showed improved activity and selectivity against Her2 positive breast cancer cells. A structure activity relationship (SAR) was summarized. Compounds 16 and 17 were also examined by western blot assay to check their effect on Her2 protein. The results reveal that the compounds could decrease the Her2 protein, which explains their selectivity to Her2 over-expressed breast cancer cells. Furthermore, the compounds inhibited the chaperone activity of small chaperone protein that could stabilize Her2 protein.

Topics: alpha-Crystallins; Anilides; Antineoplastic Agents; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Cyclohexanecarboxylic Acids; Down-Regulation; Humans; Receptor, ErbB-2; Structure-Activity Relationship; Sulfonamides

A series of COX-2 selective inhibitor nimesulide derivatives were synthesized. Their anti-cell proliferation activities were evaluated with a long-term estrogen deprived MCF-7aro (LTEDaro) breast cancer cell line, which is the biological model of aromatase inhibitor resistance for hormone-dependent breast cancer. Compared to nimesulide which inhibited LTEDaro cell proliferation with an IC(50) at 170.30 microM, several new compounds showed IC(50) close to 1.0 microM.

Topics: Antineoplastic Agents; Aromatase Inhibitors; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Cyclooxygenase 2 Inhibitors; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Humans; Molecular Structure; Stereoisomerism; Structure-Activity Relationship; Sulfonamides