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Anticancer effects of a newly-synthesized benzoxazole-derived 5-amino-2- [P-bromophenyl]-benzoxazole in breast cancer cell lines

Funda Kosova, Ozlem Temiz Arpaci, Ibrahim Tuglu, Ercument Olmez, Feyzan Ozdal Kurt, Gorkem Kismali, Zeki Ari, Mustafa Arisoy.




Abstract

We investigated the anticancer potential of 5-amino-2-[p-bromophenyl]-benzoxazole [BB] which is a new benzoxazole derivative in different breast cancer cell lines. BB was applied to estrogen receptor positive [ER+] MCF-7 and receptor negative [ER-] MDA-MB cell lines and its effects were determined by histopathological examinations, viability test [MTT], immunocytochemistry assays [Tunnel, VEGF and eNOS]. Moreover, its effects on apoptozis-related proteins such as Apaf-1, cytochrome C, caspase-3, bcl-2 and NF-κB were examined by western blot. Histopathological examinations showed that BB killed many cells for both cancer cell line while the cells lost their adhesion in MCF-7 and lost their adhesion and epiteloid morphology in MDA-MB. MTT analyses demonstrated that BB caused a clear dose depended toxic effect for both cell types. BB application resulted in an increase labeled apoptotic cells after Tunnel staining which was more obvious for MDA-MB compared to that of MCF-7. VEGF staining was decreased after BB application in both cell lines. The decrease of VEGF staining was clearer for MDA-MB compared to that of MCF-7. The status of oxidative stress was shown by eNOS immunocytochemistry which was increase after BB application in both cell lines. The levels of Apaf-1 and bcl-2 were found to be similar while caspase 9 and NF-κB levels were decreased compared to the control group after BB application for both cell lines. On the other hand, cytochrome C levels were slightly increased in MCF-7 cells while this increase was found very obvious in MDA-MB cell lines in BB groups. In conclusion, BB which is a new benzoxazole derivative have shown significant anticancer effects by increasing apoptosis and decreasing angiogenesis in MCF-7 or MDA-MB breast cancer cell lines. These effects of BB seem to be more prominent for [ER-] MDA-MB cell lines which mimic more aggressive type of breast cancer. These results suggest that BB may be useful to treat [ER-] breast cancers and may be added to treatment protocols.

Key words: Benzoxazole derivative, breast cancer, apoptosis, angiogenesis






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