2,4-dibencilaminoquinazoline induced apoptosis in three human cancer cell lines

In the search of new symmetrical derivatives with anticancer activity, we have looked for novel compounds able to induce a selective proapoptotic mechanism in cancer cells. The potential antitumoral activity of several quinazoline derivatives was evaluated in vitro examining their cytotoxic effects against human breast (HTB26), colon (HT29) and bladder (T24) cancer cell lines. Non-tumoral human cell lines were used to test the selectivity of the cytotoxic compounds against cancer cells. Several compounds showed selectivity for cancer cell lines; among them, 2,4-dibencilaminoquinazoline was chosen as the best candidate and its mechanism of action was studied in more detail. This compound was tested for its ability to induce caspase-3 activation and nuclear chromatin degradation in the three cancer cell lines. A time dependent evaluation of apoptosis was performed in the three cancer cell lines, including an expression microarray study at the points of caspase activation and chromatin degradation. 2,4-dibencilaminoquinazoline treatment produces few changes in the expression of genes as evaluated by using microarrays and RT-PCR assays. In conclusion, 2,4-di-p-bromofenilaminoquinazoline is a promising anticancer drug showing cytostatic and apoptotic effects mainly in a transcription independent manner. Keywords: Apoptosis induction, time course 12 slides were hybridized, 6 of them being dye-swap replicates of the other 6. In each slide, a treated sample and an untreated sample (negative control) were hybridized. In summary, 2 slides were used for each time point and each cell line, one of them being a dye-swap of the other.