Importance of C16 ceramide accumulation during apoptosis in prostate cancer cells

Masatoshi Eto1, Jaafar Bennouna, Oriana C Hunter

  • 1Department of Surgery/Division of Surgical Oncology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15219, USA.

Abstract

Insights

Increasing intracellular ceramide levels promotes apoptosis in prostate cancer cells. This effect is observed in both androgen-dependent cells treated with N-oleoylethanolamine and androgen-independent cells undergoing serum deprivation.

Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • Prostate adenocarcinoma is a prevalent cancer in men, often linked to androgen signaling.
  • Understanding apoptosis mechanisms is crucial for developing targeted cancer therapies.
  • Ceramides play a role in cellular signaling, including apoptosis.

Purpose of the Study:

  • To investigate the role of intracellular ceramide in apoptosis induced by androgen ablation in prostate cancer.
  • To determine if modulating ceramide levels affects apoptosis in androgen-dependent and independent prostate cancer cell lines.

Main Methods:

  • Prostate cancer cell lines (LNCaP, DU145, PC-3) were treated with N-oleoylethanolamine (NOE), sphingosine-1-phosphate (S1P), or subjected to serum deprivation.
  • Intracellular ceramide levels were manipulated pharmacologically and via serum withdrawal.
  • Apoptosis was assessed using nonyl acridine orange staining, propidium iodide staining, and cell cycle analysis.

Main Results:

  • Inhibition of acid ceramidase by NOE increased intracellular ceramide and apoptosis in androgen-dependent LNCaP cells.
  • Sphingosine-1-phosphate did not prevent apoptosis in LNCaP cells during androgen ablation.
  • Serum deprivation led to ceramide accumulation and apoptosis in androgen-independent prostate cancer cells.

Conclusions:

  • The accumulation of intracellular ceramide, rather than the ceramide/S1P balance, dictates apoptosis in LNCaP cells.
  • Elevated intracellular ceramide levels correlate strongly with apoptosis induced by serum deprivation in both androgen-dependent and independent prostate cancer cells.

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