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Acid ceramidase, an emerging target for anti-cancer and anti-angiogenesis

  • Sung Min Cho
  • Ho Jeong KwonEmail author
Review
  • 184 Downloads

Abstract

Sphingolipid metabolism plays an important role in determining the fate of a cell. Among several sphingolipid metabolites, ceramide is a key player in intracellular signal transduction. Ceramide is usually converted to various metabolites such as sphingomyelin, sphingosine, ceramide-1-phosphate, and glucosylceramide. If ceramide is accumulated in the cell, it induces apoptosis. On the other hand, its metabolite sphingosine is converted to sphingosine-1-phosphate (S1P), which promotes angiogenesis via G protein coupled receptor signaling. Therefore, the equilibrium in ceramide and S1P levels in cells plays an important role in angiogenesis as well as cell death. Acid ceramidase (AC) is a promising target protein in the development of multi-targeted anticancer drugs as its inhibition can simultaneously inhibit angiogenesis via the Akt and ERK 1/2 pathway and limit cancer growth through ceramide-induced apoptosis. Although some inhibitors of AC have been reported, they have not been proven effective for human therapy. Recent advancement in the elucidation of AC structure will facilitate the development of better inhibitors for treating human diseases.

Keywords

Acid ceramidase Ceramide Sphingosine-1-phosphate Anti-angiogenesis Anti-cancer 

Notes

Acknowledgements

This work was partly supported by Grants from the National Research Foundation of Korea (MSIP; 2015K1A1A2028365, 2015M3A9C4076321, 2016K2A9A1A03904900), the Brain Korea 21 Plus Project.

Compliance with Ethical Standards

Conflict of interest

The authors have declared that there are no conflict of interest.

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© The Pharmaceutical Society of Korea 2019

Authors and Affiliations

  1. 1.Chemical Genomics Global Research Laboratory, Department of Biotechnology, College of Life Science & BiotechnologyYonsei UniversitySeoulRepublic of Korea

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