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. The effects of trichostatin A (TSA) on gastric cancer cells have not been well characterized. This study was aimed to explore the 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, flow cytometry 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 of apoptosis-related genes, such as Bcl-2, Bax and survivin. Further study indicated that the pan-caspase inhibitor z-VAD-fmk did not inhibit the apoptosis induced by TSA, and we did not observe the cleavage of poly ADP ribose polymerase (PARP) after TSA treatment too. In addition, apoptosis inducing factor (AIF) and EndoG were found to translocate from mitochondria to nucleus in the immunofluorescence assay and the Western analysis of subcellular fractionation confirmed the result of immunofluorescence assay.


CONCLUSIONS
The apoptosis induced by TSA in gastric cancer SGC-7901 cells involves a caspase-independent pathway.
Wu
Zhi-qun
ZQ
Center of Cancer Therapy, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
Zhang
Rui
R
Chao
Connie
C
Zhang
Ji-feng
JF
Zhang
Yuan-qiang
YQ
D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000502:physiology*; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D020869:Gene Expression Profiling; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000032:analysis; D009363:Neoplasm Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000502:physiology; D051028:bcl-2-Associated X Protein / Q000032:analysis
C107489:BIRC5 protein, human; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D000077022:Survivin; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C012589:trichostatin A; D020169:Caspases