Histone deacetylase (HDAC) encoding gene expression in pancreatic cancer cell lines and cell sensitivity to HDAC inhibitors

• Type: Article in International Scientific Journal
• Date: 2008

Authors

Ouaissi, M (Author) Other; Cabral, S (Author) Other; Tavares, J (Author) FFUP; Cordeiro C da Silva (Author) FFUP; Mathieu Daude, F (Author) Other; Mas, E (Author) Other; Bernard, JP (Author) Other; Sastre, B (Author) Other; Lombardo, D (Author) Other; Ali Ouaissi (Author) Other

Journal

Title: CANCER BIOLOGY & THERAPY

Vol. 7 No. 4

Pages: 523-531

ISSN: 1538-4047

Publisher: Taylor & Francis

Indexing

ISI Web of Knowledge - 28 Citations

ISI Web of Science

Scopus - 33 Citations

Scientific classification

FOS: Medical and Health sciences > Clinical medicine

Other information

Authenticus ID: P-004-0AA

DOI: 10.4161/cbt.7.4.5480

Resumo (PT): Purpose: Multiple biochemical and molecular alterations occur in pancreatic cancer cells. In the present study, attempts were made for the first time, to explore the level of expression of members of histone deacetylase encoding genes (HDACs) in four pancreatic tumor cell lines: Panc-1, BxPC-3, SOJ-6 and MiaPaCa-2; and two non-related tumor cells: Jurkat and HeLa. Furthermore, we examined the possible relationship between the levels of HDACs expression and the sensitivity/resistance to HDAC inhibitors (TSA, Nicotinamide and Sirtinol). Methods: We have used four human pancreatic tumor cell lines and two-non related tumor cells, to evaluate the expression of HDAC encoding genes by RT-PCR and Western blot analysis. We also measured the effect of certain HDAC inhibitors (HDIs) on cell growth, cell cycle alteration, membrane phosphatidyl-serine exposure, DNA fragmentation, and mitochondrial membrane potential loss. Results: We have found that although a slight variation in the profiles of gene expression among cell lines could be evidenced, HDACs protein synthesis seem to be similar. Furthermore, the cells were equally sensitive to inhibition by Sirtinol whereas some variation in the IC50 could be seen in the case of TSA. We also demonstrate that the drugs had the capacity to induce the death of cells by apoptosis. Conclusions: Taken together, our data support the notion that the level of cell sensitivity to the HDIs might be related to the level of expression of genes such as those encoding proteins playing a role in cell cycle checkpoints control but not HDAC per se. <br> <br> <a target="_blank" href="http://www.landesbioscience.com/journals/cbt/article/5480"> Texto integral</a> <br> <br>

Abstract (EN): Purpose: Multiple biochemical and molecular alterations occur in pancreatic cancer cells. In the present study, attempts were made for the first time, to explore the level of expression of members of histone deacetylase encoding genes (HDACs) in four pancreatic tumor cell lines: Panc-1, BxPC-3, SOJ-6 and MiaPaCa-2; and two non-related tumor cells: Jurkat and HeLa. Furthermore, we examined the possible relationship between the levels of HDACs expression and the sensitivity/resistance to HDAC inhibitors (TSA, Nicotinamide and Sirtinol). Results: We have found that although a slight variation in the profiles of gene expression among cell lines could be evidenced, HDACs protein synthesis seem to be similar. Furthermore, the cells were equally sensitive to inhibition by Sirtinol whereas some variation in the IC(50) could be seen in the case of TSA. We also demonstrate that the drugs had the capacity to induce the death of cells by apoptosis. Methods: We have used four human pancreatic tumor cell lines and two-non related tumor cells, to evaluate the expression of HDAC encoding genes by RT-PCR and Western blot analysis. We also measured the effect of certain HDAC inhibitors (HDIs) on cell growth, cell cycle alteration, membrane phosphatidyl-serine exposure, DNA fragmentation and mitochondrial membrane potential loss. Conclusions: Taken together, our data support the notion that the level of cell sensitivity to the HDIs might be related to the level of expression of genes such as those encoding proteins playing a role in cell cycle checkpoints control but not HDAC per se.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9