HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Dihydroceramide desaturase knockdown impacts sphingolipids and apoptosis after photodamage in human head and neck squamous carcinoma cells.

AbstractBACKGROUND:
Dihydroceramide desaturase 1 (DES) is the enzyme responsible for converting dihydroceramide into ceramide in the de novo sphingolipid biosynthesis pathway. Dihydroceramide can inhibit ceramide channel formation to interfere with apoptosis. We have shown that following ceramide synthase knockdown, photodynamic therapy (PDT), a cancer treatment modality, is associated with decreased levels of ceramides and dihydroceramides in cells that are resistant to apoptosis.
AIM:
Here we investigated the effect of DES knockdown on the sphingolipid profile and apoptosis in human head and neck squamous carcinoma cells after PDT with the silicon phthalocyanine Pc 4.
MATERIALS AND METHODS:
Following siRNA transfection and PDT treatment, quantitative real-time polymerase chain reaction for quantification of DES mRNA, immunoblotting for protein expression, mass spectrometry for sphingolipid analysis, spectrofluorometry for caspase 3-like (DEVDase) activity, flow cytometry for apoptosis detection, and trypan blue assay for cell viability evaluation, were performed.
RESULTS:
Down-regulation of DES led to a substantial increase in levels of dihydroceramides without affecting ceramide levels. PDT-induced accumulation of individual dihydroceramides and global ceramides was increased by DES knockdown. Concomitantly, mitochondrial depolarization, DEVDase activation, late-apoptosis and cell death were attenuated by DES knockdown. Early apoptosis, however, was enhanced.
CONCLUSION:
Our findings support the following: (i) dihydroceramide reduces pro-apoptotic effects of ceramide; (ii) cells adapt to DES knockdown to become more sensitive to ceramide and early-apoptosis; (iii) DES is a potential molecular target for regulating apoptotic resistance to PDT.
AuthorsPaul Breen, Nicholas Joseph, Kyle Thompson, Jacqueline M Kraveka, Tatyana I Gudz, Li Li, Mehrdad Rahmaniyan, Jacek Bielawski, Jason S Pierce, Eric VAN Buren, Gaurav Bhatti, Duska Separovic
JournalAnticancer research (Anticancer Res) Vol. 33 Issue 1 Pg. 77-84 (Jan 2013) ISSN: 1791-7530 [Electronic] Greece
PMID23267130 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Ceramides
  • Indoles
  • RNA, Small Interfering
  • Sphingolipids
  • dihydroceramide
  • phthalocyanine Pc 4
  • Oxidoreductases
  • dihydroceramide desaturase
Topics
  • Apoptosis (drug effects, radiation effects)
  • Carcinoma, Squamous Cell (metabolism, therapy)
  • Cell Line, Tumor
  • Ceramides (metabolism, radiation effects)
  • Gene Expression Regulation, Neoplastic (drug effects, radiation effects)
  • Head and Neck Neoplasms (metabolism, therapy)
  • Humans
  • Indoles (administration & dosage)
  • Molecular Targeted Therapy
  • Oxidoreductases (antagonists & inhibitors, genetics, metabolism)
  • Photochemotherapy
  • RNA, Small Interfering
  • Sphingolipids (metabolism)

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: