Combined treatment with ABT-737 and VX-680 induces apoptosis in Bcl-2-and c-FLIP-overexpressing breast carcinoma cells

Title
Combined treatment with ABT-737 and VX-680 induces apoptosis in Bcl-2-and c-FLIP-overexpressing breast carcinoma cells
Author(s)
최정은강수환이수정민경진[민경진]우선민[우선민]권택규[권택규]
Keywords
BH3 MIMETIC ABT-737; KAPPA-B; FAMILY PROTEINS; AURORA KINASES; CANCER-CELLS; EXPRESSION; INHIBITOR; TRANSCRIPTION; SENSITIVITY; ACTIVATION
Issue Date
201503
Publisher
SPANDIDOS PUBL LTD
Citation
ONCOLOGY REPORTS, v.33, no.3, pp.1395 - 1401
Abstract
ABT-737, a BH3-mimetic small-molecule inhibitor, binds with very high affinity to Bcl-2, Bcl-xL and Bcl-w, and inhibits their activity. Aurora kinase is one of the serine/threonine kinase family members and is a vital and critical regulator of mitosis and meiosis. In the present study, we investigated the effects and mechanisms of a combined treatment of ABT-737 and VX-680 (Aurora kinase inhibitor) in human breast cancer MDA-MB-435S cells. ABT-737 plus VX-680 induced caspase-dependent apoptosis in the human breast cancer cells. Combined treatment with ABT-737 and VX-680 led to the downregulation of Bcl-2 expression at the transcriptional level and the downregulation of c-FLIP and Mcl-1 expression at the post-transcriptional level. Overexpression of Bcl-2 or c-FLIP could not block the induction of apoptosis caused by the combined treatment with ABT-737 and VX-680. However, overexpression of Mcl-1 partially inhibited the induction of apoptosis. In contrast, the combined treatment with ABT-737 and VX680 had no effect on the apoptosis in normal cells. Taken together, our study demonstrated that combined treatment with ABT-737 and VX-680 induced apoptosis in anti-apoptotic protein (Bcl-2 or c-FLIP)-overexpressing cells.
URI
http://hdl.handle.net/YU.REPOSITORY/33213http://dx.doi.org/10.3892/or.2015.3728
ISSN
1021-335X
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의과대학 > 성형외과학교실 > Articles
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