6533b854fe1ef96bd12aebdf
RESEARCH PRODUCT
Hsp72 controls bortezomib-induced HepG2 cell death via interaction with pro-apoptotic factors.
Ornella PelleritoRenza VentoPatrizia PortanovaMichela GiulianoGiuseppe CalvarusoGiovanni Tesorieresubject
Cancer ResearchProgrammed cell deathCarcinoma HepatocellularTime FactorsCellBlotting WesternApoptosisHSP72 Heat-Shock ProteinsAmino Acid Chloromethyl KetonesBortezomibCell Line TumormedicineHumansImmunoprecipitationProtease Inhibitorscardiovascular diseasesCaspasebcl-2-Associated X ProteinOncogenebiologyBortezomibReverse Transcriptase Polymerase Chain ReactionLiver NeoplasmsApoptosis Inducing Factorproteasome inhibitor hepatocarcinoma apoptosisGeneral MedicineCell cycleBoronic Acidsmedicine.anatomical_structureApoptotic Protease-Activating Factor 1OncologyApoptosisPyrazinesProteasome inhibitorCancer researchbiology.proteinTumor Suppressor Protein p53Apoptosis Regulatory Proteinsmedicine.drugProtein Bindingdescription
The proteasome inhibitor bortezomib is an efficacious inducer of apoptosis in the hepatoma HepG2 cell line. This study shows that bortezomib increased in these cells the level of the survival factor Hsp72 in a time- and dose-dependent manner. In a first phase of treatment, Hsp72 rapidly increased so that at 24 h of incubation with 50 nM bortezomib its level was approximately five-fold higher than the control. In this phase Hsp72 seemed to play a role in preventing HepG2 cell death, since it interacted with and sequestered the pro-apoptotic factors p53, AIF, Bax and Apaf-1. During a second day of treatment, although the nuclear levels of Hsp72, p53 and AIF increased, the interaction of Hsp72 with these factors diminished. In addition, bortezomib induced the activation of caspases, which stimulated Hsp72 degradation. In conclusion, in the second day of treatment with bortezomib the protective ability of Hsp72 decreased thus favouring the appearance of apoptosis.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2007-07-06 |