Biochemical and Biophysical Research Communications 2015-08-28

Targeting ceramide metabolic pathway induces apoptosis in human breast cancer cell lines.

Helen Shiphrah Vethakanraj, Thabraz Ahmed Babu, Ganesh Babu Sudarsanan, Prabhu Kumar Duraisamy, Sekar Ashok Kumar

文献索引：Biochem. Biophys. Res. Commun. 464 , 833-9, (2015)

全文：HTML全文

摘要

The sphingolipid ceramide is a pro apoptotic molecule of ceramide metabolic pathway and is hydrolyzed to proliferative metabolite, sphingosine 1 phosphate by the action of acid ceramidase. Being upregulated in the tumors of breast, acid ceramidase acts as a potential target for breast cancer therapy. We aimed at targeting this enzyme with a small molecule acid ceramidase inhibitor, Ceranib 2 in human breast cancer cell lines MCF 7 and MDA MB 231. Ceranib 2 effectively inhibited the growth of both the cell lines in dose and time dependant manner. Morphological apoptotic hallmarks such as chromatin condensation, fragmented chromatin were observed in AO/EtBr staining. Moreover, ladder pattern of fragmented DNA observed in DNA gel electrophoresis proved the apoptotic activity of Ceranib 2 in breast cancer cell lines. The apoptotic events were associated with significant increase in the expression of pro-apoptotic genes (Bad, Bax and Bid) and down regulation of anti-apoptotic gene (Bcl 2). Interestingly, increase in sub G1 population of cell cycle phase analysis and elevated Annexin V positive cells after Ceranib 2 treatment substantiated its apoptotic activity in MCF 7 and MDA MB 231 cell lines. Thus, we report Ceranib 2 as a potent therapeutic agent against both ER(+) and ER(-) breast cancer cell lines. Copyright © 2015 Elsevier Inc. All rights reserved.