Histone deacetylase inhibitor trichostatin A induced caspase-independent apoptosis in human gastric cancer cell

Background Histone deacetylase inhibitors(HDACIs)have been reported to induce apoptosis in cancer cells.Theeffects of trichostatin A(TSA)on gastric cancer cells have not been well characterized.This study was aimed to explorethe effects and mechanisms of TSA on human gastric cancer SGC-7901 cells.Methods The cells were treated with TSA and analyzed by cell proliferation assay,Western blot,TUNEL assay,flowcytometry by fluorescein isothiocyanate(FITC)conjugated with Annexin V and PI staining,immunofluorescence analysis,analysis of subcellular fractionation,gene chips and real time polymerase chain reaction(PCR).Results TSA could inhibit cell growth and induced apoptosis in gastric cancer SGC-7901 cells through the regulation ofapoptosis-related genes,such as Bcl-2,Bax and survivin.Further study indicated that the pan-caspase inhibitorz-VAD-fmk did not inhibit the apoptosis induced by TSA,and we did not observe the cleavage of poly ADP ribosepolymerase(PARP)after TSA treatment too.In addition,apoptosis inducing factor(AIF)and EndoG were found totranslocate from mitochondria to nucleus in the immunofluorescence assay and the Western analysis of subcellularfractionation confirmed the result of immunofluorescence assay.Conclusions The apoptosis induced by TSA in gastric cancer SGC-7901 cells involves a caspase-independentpathway.