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Research Paper

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

M. Ouaïssi, S. Cabral, J. Tavares, A. Cordeiro da Silva, F. Mathieu-Daude, E. Mas, JP Bernard, B. Sastre, D. Lombardo and A. Ouaissi

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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.

Authors

M. Ouaïssi

Hôpital Timone, Marseille, France

S. Cabral

Universidade do Porto, Portuga

J. Tavares

Universidade do Porto, Portuga

A. Cordeiro da Silva

Universidade do Porto, Portuga

F. Mathieu-Daude

INSERM, IRD UR008, centre IRD de Montpellier, France

E. Mas

Faculté de Médecine-Timone, Marseille, France

JP Bernard

Faculté de Médecine-Timone, Marseille, France

B. Sastre

Hôpital Timone, Marseille, France

D. Lombardo

Faculté de Médecine-Timone, Marseille, France

A. Ouaissi

Instituto de Biologia Molecular e Celular, Universidade do Porto, Portugal

Purchase article for $19

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