| Induction of cell cycle arrest and DNA damage by the HDAC inhibitor panobinostat (LBH589) and the lipid peroxidation end product 4-hydroxynonenal in prostate cancer cells. | |
| | |
MedLine Citation:
|
PMID: 21078383 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
|
Histone deacetylase inhibitors (HDACIs) are promising antineoplastic agents for the treatment of cancer. Here we report that the lipid peroxidation end product 4-hydroxynonenal (HNE) significantly potentiates the anti-tumor effects of the HDAC inhibitor panobinostat (LBH589) in the PC3 prostate cancer cell model. Panobinostat and HNE inhibited proliferation of PC3 cells and the combination of the two agents resulted in a significant combined effect. Cell cycle analysis revealed that both single agents and, to a greater extent, their combined treatment induced G2/M arrest, but cell death occurred in the combined treatment only. Furthermore, HNE and, to a greater extent, the combined treatment induced dephosphorylation of Cdc2 leading to progression into mitosis as confirmed by α-tubulin/DAPI staining and phospho-histone H3 (Ser10) analysis. To evaluate possible induction of DNA damage we utilized the marker phosphorylated histone H2A.X. Results showed that the combination of panobinostat and HNE induced significant DNA damage concomitant with the mitotic arrest. Then, by using androgen receptor (AR)-expressing PC3 cells we observed that the responsiveness to HNE and panobinostat was independent of the expression of functional AR. Taken together, our data suggest that HNE potentiates the antitumoral effect of the HDACI panobinostat in prostate cancer cells. |
| | |
Authors:
|
Piergiorgio Pettazzoni; Stefania Pizzimenti; Cristina Toaldo; Paula Sotomayor; Luigina Tagliavacca; Song Liu; Dan Wang; Rosalba Minelli; Leigh Ellis; Peter Atadja; Eric Ciamporcero; Mario Umberto Dianzani; Giuseppina Barrera; Roberto Pili |
Related Documents
:
|
17879953 - P63 in prostate biology and pathology. 15221243 - Induction of anoikis by doxazosin in prostate cancer cells is associated with activatio... 15518543 - Tumor cells resistant to a microtubule-depolymerizing hemiasterlin analogue, hti-286, h... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-11-13 |
Journal Detail:
|
Title: Free radical biology & medicine Volume: 50 ISSN: 1873-4596 ISO Abbreviation: Free Radic. Biol. Med. Publication Date: 2011 Jan |
Date Detail:
|
Created Date: 2011-01-10 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 8709159 Medline TA: Free Radic Biol Med Country: United States |
Other Details:
|
Languages: eng Pagination: 313-22 Citation Subset: IM |
Copyright Information:
|
Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
|
Department of Medicine and Experimental Oncology, Section of General Pathology, University of Turin, Turin, Italy. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
| Grant Support | |
ID/Acronym/Agency:
|
P50 CA58236/CA/NCI NIH HHS |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Arsenic methylation efficiency increases during the first trimester of pregnancy independent of fola...
Next Document: Human prostaglandin H synthase (hPHS)-1- and hPHS-2-dependent bioactivation, oxidative macromolecula...