Herein, we report our examination of the anti-
breast cancer activity of a novel synthetic compound, 7-(benzylamino)-1, 3, 4, 8-tetrahydropyrrolo [4, 3, 2-de]quinolin-8(1H)-one (
BA-TPQ). This agent is an analog of a naturally occurring marine compound, and was found to be the most active out of more than 40 related compounds. We investigated the in vitro activity of
BA-TPQ on the survival, proliferation, and apoptosis of
breast cancer cells using the MTT and BrdUrd assays, and
Annexin/
Annexin-PI staining and flow cytometry. The in vivo anti-
cancer effects of
BA-TPQ were evaluated in xenograft models of
breast cancer. Finally, the mechanisms of action of the compound were also assessed by
cDNA microarrays, RT-PCR and Western blotting. In a dose-dependent manner,
BA-TPQ inhibited cell growth and induced apoptosis and cell cycle arrest in human MCF-7 and MDA-MB-468
breast cancer cells in vitro, and showed in vivo efficacy in mice bearing MCF-7 or MDA-MB-468 xenograft
tumors. We demonstrated that
BA-TPQ modifies the expression of numerous molecules involved in cell cycle progression and apoptosis. Similar changes in
protein expression were observed in vitro and in vivo, as determined by examination of cells and excised xenograft
tumors. Our preclinical data indicate that
BA-TPQ is a potential therapeutic agent for
breast cancer that has multiple
hormone-, Her2-, and p53-independent mechanisms of action, providing a basis for further development of the compound as a novel
anticancer agent.