AI Article Synopsis

  • Ceramide, a pro-apoptotic molecule, is converted to sphingosine 1 phosphate by acid ceramidase, which is upregulated in breast tumors, making it a potential target for therapy.
  • Researchers tested a small molecule inhibitor, Ceranib 2, on breast cancer cell lines MCF 7 and MDA MB 231, finding it effectively inhibited growth in a dose and time-dependent way.
  • Ceranib 2 induced apoptosis, evidenced by DNA fragmentation and increased expression of pro-apoptotic genes while decreasing anti-apoptotic gene expression, suggesting its potential as a therapeutic agent for different breast cancer types.

Article Abstract

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.

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http://dx.doi.org/10.1016/j.bbrc.2015.07.047DOI Listing

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