TSA-induced cell death in prostate cancer cell lines is caspase-2 dependent and involves the PIDDosome

Agshin F Taghiyev; Natalya V Guseva; Rebecca A Glover; Oskar W Rokhlin; Michael B Cohen

doi:10.4161/cbt.5.9.3168

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TSA-induced cell death in prostate cancer cell lines is caspase-2 dependent and involves the PIDDosome

Journal article

Peer reviewed

TSA-induced cell death in prostate cancer cell lines is caspase-2 dependent and involves the PIDDosome

Agshin F Taghiyev, Natalya V Guseva, Rebecca A Glover, Oskar W Rokhlin and Michael B Cohen

Cancer biology & therapy, Vol.5(9), pp.1199-1205

09/01/2006

DOI: 10.4161/cbt.5.9.3168

PMID: 17110788

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Abstract

The histone deacetylase inhibitor Trichostatin A (TSA) has previously been found to induce caspase activity in the human prostate cancer cell lines DU145 and LNCaP. TSA treatment resulted in the release of cytochrome c and Smac/DIABLO from mitochondria in DU145, and activation of caspase-9 in both cell lines. We concluded that TSA mediated its effect via the mitochondrial pathway. The aim of the current study was to determine how TSA initiated the caspase cascade. The results revealed that caspase-2 plays an important role in TSA-induced apoptosis. Inhibition of caspase-2 by siRNA or expression of caspase-2dn substantially decreased caspase activity after TSA treatment in both cell lines, siRNA caspase-2 also inhibited TSA-induced cell death. Caspase-2 acts upstream of caspase-8 and -9 and mediates mitochondrial cytochrome c release. Coimmunoprecipitation experiments show that caspase-2 formed protein complexes with RADD/RAIDD and PIDD. Together, these data indicate that caspase-2 initiates caspase cascade after TSA treatment and involves the formation of the PIDDosome.

Carrier Proteins - genetics

Carrier Proteins - metabolism

Caspase 2 - genetics

Caspase 2 - metabolism

Caspase 8 - metabolism

Caspase 9 - metabolism

Cell Death - drug effects

Cell Line, Tumor

CRADD Signaling Adaptor Protein - metabolism

Cytochromes c - metabolism

Death Domain Receptor Signaling Adaptor Proteins

Enzyme Activation - drug effects

Histone Deacetylase Inhibitors

Humans

Hydroxamic Acids - pharmacology

Male

Mitochondria - drug effects

Mitochondria - metabolism

Prostatic Neoplasms - drug therapy

Prostatic Neoplasms - genetics

Prostatic Neoplasms - metabolism

Prostatic Neoplasms - pathology

RNA, Small Interfering - genetics

Transfection

Details

Title: Subtitle: TSA-induced cell death in prostate cancer cell lines is caspase-2 dependent and involves the PIDDosome
Creators: Agshin F Taghiyev - University of Iowa
Natalya V Guseva
Rebecca A Glover
Oskar W Rokhlin
Michael B Cohen
Resource Type: Journal article
Publication Details: Cancer biology & therapy, Vol.5(9), pp.1199-1205
DOI: 10.4161/cbt.5.9.3168
PMID: 17110788
NLM abbreviation: Cancer Biol Ther
ISSN: 1538-4047
eISSN: 1555-8576
Grant note: CA87617 / NCI NIH HHS
Language: English
Date published: 09/01/2006
Academic Unit: Pathology; Biology
Record Identifier: 9984647058402771

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