Histone deacetylase (HDAC) encoding gene expression in pancreatic cancer cell lines and cell sensitivity to HDAC inhibitors.
OBJECTIVE
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.
Ouaïssi
M
M
Service de chirurgie Digestive et Oncologique, Hôpital Timone, Marseille, France.
Cabral
S
S
Tavares
J
J
da Silva
A Cordeiro
AC
Mathieu Daude
F
F
Mas
E
E
Bernard
Jp
J
Sastre
B
B
Lombardo
D
D
Ouaissi
Ali
A
D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics; D001549:Benzamides / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015870:Gene Expression; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000235:genetics*; D006801:Humans; D009284:Naphthols / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000235:genetics
D001549:Benzamides; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D009284:Naphthols; C439060:sirtinol; D006655:Histone Deacetylases