HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Autophagy is increased in prostate cancer cells overexpressing acid ceramidase and enhances resistance to C6 ceramide.

Abstract
Acid ceramidase (AC) overexpression has been observed in prostate cancer cell lines and primary tumors, and contributes to resistance to chemotherapy and radiation. The consequence of AC overexpression is the ability to convert ceramide, which is often produced as a proapoptotic response to stress, to sphingosine, which can then be converted to the prosurvival molecule sphingosine-1-phosphate. In addition to their ability to metabolize ceramide produced in response to stress, we show here that prostate cancer cell lines overexpressing AC also have increased lysosomal density and increased levels of autophagy. Furthermore, pretreatment with 3-methyladenine restores sensitivity of these cells to treatment with C(6) ceramide. We also observed increased expression of the lysosomal stabilizing protein KIF5B and increased sensitivity to the lysosomotropic agent LCL385. Thus, we conclude that AC overexpression increases autophagy in prostate cancer cells, and that increased autophagy enhances resistance to ceramide.
AuthorsL S Turner, J C Cheng, T H Beckham, T E Keane, J S Norris, X Liu
JournalProstate cancer and prostatic diseases (Prostate Cancer Prostatic Dis) Vol. 14 Issue 1 Pg. 30-7 (Mar 2011) ISSN: 1476-5608 [Electronic] England
PMID21116286 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Antineoplastic Agents
  • Ceramides
  • Acid Ceramidase
Topics
  • Acid Ceramidase (metabolism)
  • Antineoplastic Agents (pharmacology)
  • Autophagy
  • Cell Line, Tumor
  • Ceramides (metabolism, pharmacology)
  • Drug Resistance, Neoplasm
  • Humans
  • Male
  • Prostatic Neoplasms (drug therapy, enzymology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: