6533b834fe1ef96bd129d8a2
RESEARCH PRODUCT
Sodium phenylbutyrate induces apoptosis in human retinoblastoma Y79 cells: The effect of combined treatment with the topoisomerase I-inhibitor topotecan
Giuseppe CalvarusoMaria CarabillòAntonella D’anneoMarianna LauricellaGiovanni TesoriereRenza VentoMichela Giulianosubject
Cancer ResearchProgrammed cell deathCell SurvivalBlotting WesternApoptosisPhenylbutyrateHistonesSettore BIO/10 - BiochimicamedicineTumor Cells CulturedHumansretinoblastoma apoptosis sodium phenylbutirateViability assayEnzyme InhibitorsbiologyCaspase 3TopoisomeraseRetinoblastomaSodium phenylbutyrateAcetylationDrug SynergismCell cyclePhenylbutyrateseye diseasesEnzyme ActivationOncologyProto-Oncogene Proteins c-bcl-2ApoptosisCaspasesbiology.proteinCancer researchTopotecanDrug Therapy CombinationTopoisomerase I InhibitorsTumor Suppressor Protein p53Topotecanmedicine.drugdescription
Our results demonstrate that sodium phenylbutyrate, a compound with a low degree of toxicity, exerted a cytotoxic effect on human retinoblastoma Y79 cells in a time- and dose-dependent manner. Treatment of Y79 cells for 72 h with phenylbutyrate reduced cell viability by 63% at 2 mM and 90% at 4 mM. Cell death caused by phenylbutyrate exhibited the typical features of apoptosis, as shown by light and fluorescent microscopy. Western blot analysis demonstrated that exposure of Y79 cells to phenylbutyrate decreased the level of the antiapoptotic factor Bcl-2 and induced the activation of caspase-3, a key enzyme in the execution phase of apoptosis. Moreover, treatment with phenylbutyrate markedly increased the level of acetylated histone-H3. Combined treatment with phenylbutyrate and topotecan, a topoisomerase I-inhibitor, resulted in a clear synergistic effect. We suggest that the effects exerted by phenylbutyrate on Y79 cells essentially depend on modifications of gene expression consequent to histone hyperacetylation.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2001-05-15 |