Marker genes to predict sensitivity to FK228, a histone deacetylase inhibitor

Ornithine decarboxylase activity in tumor cell lines correlates with sensitivity to cell death induced by histone deacetylase inhibitors

“…Cell lines with high levels of ODC activity were more sensitive to HDAC inhibitor -induced apoptosis, and this correlation was In addition, the ability of TSA to further induce ODC activity correlated with increased sensitivity to HDAC inhibitor -induced apoptosis. In microarray studies, HDAC inhibitor treatment of various cell lines induces ODC mRNA (46,47). We found that TSA treatment increased ODC protein levels (data not shown).…”

Histone deacetylase inhibitors: molecular mechanisms of action

“…Early differential display experiments with lymphoid cell lines cultured with TSA showed that only 2% of 340 genes examined were altered in their expression, either increased or decreased, compared to untreated cells (Van Lint et al, 1996). Recent studies using cDNA arrays showed as many as 7-10% of genes were altered in their expression in cell lines of leukemia, multiple myeloma, and carcinomas of colon, bladder, kidney, prostate and breast, cultured for up to 48 h with butyrate, TSA, MS-275, vorinostat or FK228 (depsipeptide) using twofold change as the cut-off value (Chambers et al, 2003;Glaser et al, 2003;Mitsiades et al, 2004;Peart et al, 2005;Sasakawa et al, 2005). The time of culture, concentration and the HDACi used affect the number of genes detected with altered transcription.…”

“…The time of culture, concentration and the HDACi used affect the number of genes detected with altered transcription. Short time points (Chambers et al, 2003;Mitsiades et al, 2004;Sasakawa et al, 2005) and low concentrations (Glaser et al, 2003) (Glaser et al, 2003;Gray et al, 2004;Mitsiades et al, 2004;Peart et al, 2005;Sasakawa et al, 2005). In these several studies, it has been found that HDACi induce about as many genes as are repressed.…”

Systemic co-administration of depsipeptide selectively targets transfection enhancement to specific tissues and cell types

“…2,4 The HDAC inhibitor, depsipeptide, can induce apoptosis, 3 growth inhibition 1 and differentiation of tumor cells. 4,14 Furthermore, direct intratumoral administration of depsipeptide can significantly increase both the levels of expression of delivered genes and the antitumor effects produced by non-viral approaches in mice. 9,24 Specifically, local administration of depsipeptide with HVJ liposomes directly into subcutaneous B16 melanoma tumors increased reporter gene activity 3.3-fold in injected tumors.…”

“…Depsipeptide differentially affects tumor cells versus normal cells. 4,14,15 Therefore, we assessed whether i.v. co-injection of depsipeptide with PEI:DNA complexes encoding the wild-type human p53 gene produced differential effects on human p53 expression in metastatic tumors versus in adjacent normal cells within tumor-bearing mice.…”