Abstract B36: A 1,5-diheteroarylpenta-1,4-dien-3-one inhibits TNBC cell growth by blocking AKT/mTOR/P70S6K pathway

One in 8 women will develop breast cancer during the course of her life. Recent developments in the field of drug development have provided a significant increase in progression free survival and decrease in mortality of this disease. However, one of the main problems in breast cancer remains the development of resistance to current treatments and relapse of the disease. Moreover, there is no known target for the treatment of the triple negative breast cancers (TNBC) subset, which is more aggressive than the other types of the disease. Therefore, it is imperative to develop new drugs that can block the activity of pro-survival signaling within the cancer cells and inhibit their growth, particularly in the TNBC subset. In an attempt to identify such drugs, we screened a panel of 13 compounds, containing the general structure of 1,5-diheteroarylpenta-1,4-dien-3-one (compounds 34 to 46), for their effectiveness in inhibiting the growth of both TNBC and ER+ breast cancers. The IC50s for these compounds were in the range of 63 to 8346 nM against various breast cancer cell lines. Interestingly, the most potent compound (# 34), (1E,4E)-1,5-bis(1-pentan-2-yl)-1H-imidazol-2-yl)penta-1,4-dien-3-one, showed its highest growth inhibitory activity in the TNBC cell line, MDA-MB-231, while also being effective in inhibiting the growth of ER+ cell lines to a lesser extent. Further investigations were then focused on this TNBC cell line. The mechanism of action of compound 34 was investigated...
Source: Molecular Cancer Therapeutics - Category: Cancer & Oncology Authors: Tags: Chemical Biology: Poster Presentations - Proffered Abstracts Source Type: research