Original articleGeneral thoracicEffectiveness of Trichostatin A as a Potential Candidate for Anticancer Therapy in Non–Small-Cell Lung Cancer
Section snippets
Reagents
Dulbecco’s modified Eagle’s medium, RPMI 1640 medium, fetal bovine serum, trypsin, phosphate-buffered saline, penicillin-streptomycin, and glutamate were purchased from Invitrogen Life Technologies (Carlsbad, CA). Trichostatin A was purchased from Calbiochem (San Diego, CA). Bovine serum albumin and soybean trypsin inhibitor were from Sigma Chemical Company (St. Louis, MO). Proto-gel was from National Diagnostic (Atlanta, GA). Anti-acetylated histone H4 was from Upstate Biotechnology (Lake
Trichostatin A Possesses Antiproliferative Activity Against Non–Small-Cell Lung Cancer Cells
Proliferation in all four NSCLC cell lines was inhibited by TSA in a dose-dependent fashion (Table 1). We determined that effective growth inhibition by TSA occurred within 48 hours. After 48 hours of incubation, the IC50 of the two squamous lines (Calu-1 and H520) was 0.034 and 0.046 μmol/L, respectively. The IC50 of the two adenocarcinoma lines (H441 and H23) was 0.012 and 0.054 μmol/L, respectively. The mean IC50 for all four NSCLC lines was 0.036 ± 0.019 μmol/L. In contrast to the tumor
Comment
The antiproliferative properties of TSA were characterized in four NSCLC lines and in one NLF line. Differential effects in normal versus tumor cells were observed because certain concentrations of TSA produced significant cell death in NSCLC cells compared with normal controls, suggesting the possibility of a therapeutic window. The IC50, as determined on cell growth inhibition assay, is well below the physiologic dose. However, the significance of our observation needs to be further evaluated
References (47)
- et al.
Isolation and characterization of mammalian HDAC10, a novel histone deacetylase
J Biol Chem
(2002) - et al.
Effects of cell density and trichostatin A on the expression of HDAC1 and p57Kip2 in Hep 3B cells
Biochem Biophys Res Commun
(1998) - et al.
Direct inhibition of the expression of cyclin D1 gene by sodium butyrate
Biochem Biophys Res Commun
(1996) - et al.
Histone deacetylase inhibition selectively alters the activity and expression of cell cycle proteins leading to specific chromatin acetylation and antiproliferative effects
J Biol Chem
(1999) - et al.
Coactivator and corepressor complexes in nuclear receptor function
Curr Opin Genet Dev
(1999) - et al.
Induction of apoptosis of lung and esophageal cancer cells treated with the combination of histone deacetylase inhibitor (Trichostatin A) and protein kinase C inhibitor (Calphostin C)
J Thorac Cardiovasc Surg
(2005) - et al.
Trichostatin A induces morphological changes and gasoline expression by inhibiting histone deacetylase in human carcinoma cell lines
Exp Cell Res
(1994) - et al.
Epigenetic regulation of gasoline expression in human breast cancer cells
Exp Cell Res
(1999) - et al.
Homozygous loss of the cyclin-dependent kinase 4-inhibitor (p16) gene in human leukemias
Blood
(1994) - et al.
Inhibition of mitogenesis in Balb/c-3T3 cells by Trichostatin AMultiple alterations in the induction and activation of cyclin-cyclin-dependent kinase complex
J Biol Chem
(2000)