Importance of C16 ceramide accumulation during apoptosis in prostate cancer cells

Masatoshi Eto, Jaafar Bennouna, Oriana C. Hunter, Michael T. Lotze, Andrew A. Amoscato

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Aim: Adenocarcinoma of the prostate is one of the most frequently diagnosed non-cutaneous cancers and the second leading cause of cancer-related deaths among men in the United States. To fully understand the role of ceramide during apoptosis induced by androgen ablation, we modified the levels of intracellular ceramide by pharmacological agents as well as through serum deprivation in androgen-dependent and independent cell lines. Methods: Ceramide levels were modified using N-oleoylethanolamine (NOE), sphingosine-1-phosphate (S1P) as well as through serum deprivation, in LNCaP, DU145 and PC-3 prostate cancer cells. Various methods including nonyl acridine orange staining, propidium iodide staining/cell cycle analysis and lipid analysis were utilized. Results: Our results demonstrate that the inhibition of acid ceramidase by NOE enhances the intracellular ceramide levels induced by androgen ablation in androgen-dependent LNCaP cells, and is accompanied by an increase in apoptotic cells. Sphingosine 1-phosphate had no effect in rescuing LNCaP cells from apoptosis induced by androgen ablation. Our results also show that serum deprivation causes intracellular ceramide accumulation and apoptosis in androgen-independent prostate cancer cells. Conclusions: Our studies indicate that the increase in intracellular ceramide itself, but not the balance between ceramide and S1P, determines whether LNCaP cells undergo apoptosis. Our results also show that the increase in intracellular ceramide strongly correlates with apoptosis induced by serum deprivation even in androgen-independent prostate cancer cell lines.

Original languageEnglish
Pages (from-to)148-156
Number of pages9
JournalInternational Journal of Urology
Volume13
Issue number2
DOIs
Publication statusPublished - Feb 1 2006

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Ceramides
Androgens
Prostatic Neoplasms
Apoptosis
Serum
Acid Ceramidase
Staining and Labeling
Cell Line
Acridine Orange
Second Primary Neoplasms
Propidium
N-palmitoylsphingosine
Prostate
Cell Cycle
Adenocarcinoma
Pharmacology
Lipids
sphingosine 1-phosphate
Neoplasms

All Science Journal Classification (ASJC) codes

  • Urology

Cite this

Importance of C16 ceramide accumulation during apoptosis in prostate cancer cells. / Eto, Masatoshi; Bennouna, Jaafar; Hunter, Oriana C.; Lotze, Michael T.; Amoscato, Andrew A.

In: International Journal of Urology, Vol. 13, No. 2, 01.02.2006, p. 148-156.

Research output: Contribution to journalArticle

Eto, Masatoshi ; Bennouna, Jaafar ; Hunter, Oriana C. ; Lotze, Michael T. ; Amoscato, Andrew A. / Importance of C16 ceramide accumulation during apoptosis in prostate cancer cells. In: International Journal of Urology. 2006 ; Vol. 13, No. 2. pp. 148-156.
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