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Saturated Fatty Acids Induce Ceramide-associated Macrophage Cell Death
Published on: October 31, 2017
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.
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.
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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