Cancer Chemotherapy and Pharmacology

, Volume 71, Issue 1, pp 13–20 | Cite as

Therapeutic potential of targeting ceramide/glucosylceramide pathway in cancer

Review Article

Abstract

Sphingolipids including ceramides and its derivatives such as ceramide-1-phosphate, glucosylceramide (GlcCer), and sphingosine-1-phosphate are essential structural components of cell membranes. They now recognized as novel bioeffector molecules which control various aspects of cell growth, proliferation, apoptosis, and drug resistance. Ceramide, the central molecule of sphingolipid metabolism, generally mediates anti-proliferative responses such as inhibition of cell growth, induction of apoptosis, and/or modulation of senescence. There are two major classes of sphingolipids. One of them is glycosphingolipids which are synthesized from the hydrophobic molecule, ceramide. GlcCer, generated by glucosylceramide synthase (GCS) that transfers the glucose from UDP-glucose to ceramide, is an important glycosphingolipid metabolic intermediate. GCS regulates the balance between apoptotic ceramide and antiapoptotic GlcCer. Downregulation or inhibition of GCS results in increased apoptosis and decreased drug resistance. The mechanism underlying the drug resistance which develops with increased glucosylceramide expression is associated with P-glycoprotein. In various types of cancers, overexpression of GCS has been observed which renders GCS a good target for the treatment of cancer. This review summarizes our current knowledge on the structure and functions of glucosylceramide synthase and glucosylceramide and on the roles of glucosylceramide synthase in cancer therapy and drug resistance.

Keywords

Glucosylceramide synthase Cancer therapy Glucosylceramide Drug resistance Ceramide Sphingolipid 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Melis Kartal Yandım
    • 1
  • Elif Apohan
    • 1
    • 2
  • Yusuf Baran
    • 1
  1. 1.Department of Molecular Biology and Genetics, Faculty of Scienceİzmir Institute of TechnologyUrla, IzmirTurkey
  2. 2.Department of Biology, Faculty of Art and Scienceİnönü UniversityMalatyaTurkey

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