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N-Acyl Taurines are Anti-Proliferative in Prostate Cancer Cells
Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
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2012 (English)In: Lipids, ISSN 0024-4201, E-ISSN 1558-9307, Vol. 47, no 4, 355-361 p.Article in journal (Refereed) Published
Abstract [en]

Endocannabinoids have been implicated in cancer development and cause heterogenous effects in tumor cells, by inducing apoptosis, reducing migration, causing anti-angiogenic activity and alterations in the cell cycle resulting in growth arrest. Recently, several novel amides of fatty acids that are structurally related to endocannabinoids have been isolated from mammalian sources, although the functions of these fatty amides are not well studied. One group of these novel fatty acid amides are the N-acyl taurines (fatty acids conjugated to the amino acid taurine). This study examined if N-acyl taurines, specifically N-arachidonoyl taurine and N-oleoyl taurine could function in a similar way to endocannabinoids and result in cell cycle alterations or growth arrest in the human prostate adenocarcinoma cell line PC-3. PC-3 cells were treated with various concentrations of N-arachidonoyl taurine and N-oleoyl taurine and cell proliferation and viability was measured using resazurin and colony formation assays. Effects of N-acyl taurines on the cell cycle was measured using FACS analysis. Treatment with N-arachidonoyl taurine and N-oleoyl taurine resulted in a significant reduction in proliferation of PC-3 cells, even at concentrations as low as 1 mu M. Treatment with N-oleoyl taurine resulted in an increased number of cells in the subG1 population, suggesting apoptosis, and a lower number of cells in S-phase of the cell cycle. In summary, our results show that novel biologically active lipids, the N-acyl taurines, result in reduced proliferation in PC-3 cells.

Place, publisher, year, edition, pages
2012. Vol. 47, no 4, 355-361 p.
Keyword [en]
N-Arachidonoyl taurine, N-Oleoyl taurine, Fatty acid amide hydrolase, N-Acyl amino acids, PC-3 cells, Cell proliferation
National Category
Biological Sciences
Research subject
Molecular Genetics
Identifiers
URN: urn:nbn:se:su:diva-76070DOI: 10.1007/s11745-011-3639-9ISI: 000302095400002OAI: oai:DiVA.org:su-76070DiVA: diva2:525513
Note

5

Available from: 2012-05-08 Created: 2012-05-08 Last updated: 2017-12-07Bibliographically approved
In thesis
1. Studies of bioactive lipids in cancer
Open this publication in new window or tab >>Studies of bioactive lipids in cancer
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Lipids are a broad class of molecules that, besides being a major form of energy storage and components of cell membranes, act as bioactive signalling molecules. N-acyl taurines are structurally related to endocannabinoids that are known to exert antiproliferative actions in a variety of cancer cells. We have evaluated the cytotoxicity of N-oleoyl taurine and N-arachidonoyl taurine and found N-acyl taurines to reduce proliferation of prostate cancer cells.

The sphingolipids ceramide and sphingosine act as tumour suppressors. We found selenite treatment to cause reduced viability, induction of neutral sphingomyelinase activity and accumulation of ceramide in the liver cancer cells. Inhibition of sphingosine kinase 1 (SK1) sensitized the cells to selenite treatment with regards to ceramide accumulation, arrest of cells in the G1/S phases of the cell cycle and formation of reactive oxygen species. Whereas combined selenite treatment and SK1 inhibition synergistically reduced the number of viable cells, the non-tumorigenic hepatocyte cell line, remained unaffected.

Furthermore, we studied the involvement of sphingolipid metabolism in bladder cancer cells treated with Bacillus Calmette-Guérin (BCG), and found BCG to induce formation of nitric oxide and upregulation of nitric oxide synthase 2 as well as SK1 protein levels. Additionally, pharmacological inhibition of SK1 enhanced the viability reduction, ceramide accumulation and induction of apoptosis observed following BCG treatment.

In conclusion, our findings have shown that N-acyl taurines exert antiproliferative effects on prostate cancer cells. Furthermore, sphingolipids were shown to be involved in cytotoxic treatment with selenite and BCG in liver cancer and bladder cancer cells respectively, and inhibition of SK1 increased the cytotoxicity. Our findings raise the possibility that modulation of ceramide-metabolizing enzymes could be used to enhance the effects of selenite and BCG in these cancer cell types.

Place, publisher, year, edition, pages
Stockholm: Department of Genetics, Microbiology and Toxicology, Stockholm University, 2012. 67 p.
Keyword
Lipids, Sphingolipids, N-acyl amino acids, cancer
National Category
Biological Sciences
Research subject
Molecular Genetics
Identifiers
urn:nbn:se:su:diva-79024 (URN)978-91-7447-548-7 (ISBN)
Public defence
2012-09-26, lecture room G, Arrheniuslaboratorierna, Svante Arrhenius väg 20 C, Stockholm, 13:00 (English)
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Note

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Manuscript. Paper 4: Manuscript.

Available from: 2012-09-04 Created: 2012-08-23 Last updated: 2012-08-27Bibliographically approved

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