Intrinsic apoptotic and thioredoxin pathways in human prostate cancer cell response to histone deacetylase inhibitor Journal Article

   


Authors: Xu, W.; Ngo, L.; Perez, G.; Dokmanovic, M.; Marks, P. A.
Article Title: Intrinsic apoptotic and thioredoxin pathways in human prostate cancer cell response to histone deacetylase inhibitor
Abstract: There is a great need to develop better mechanism-based therapies for prostate cancer. In this investigation, we studied four human prostate cancer cell lines, LNCaP, DU145, LAPC4, and PC3, which differ in response to the histone deacetylase inhibitor, suberoylanilide hydroxamic acid (vorinostat), a new anticancer drug. Examining the role of intrinsic mitochondrial caspase-dependent apoptosis and caspase-independent, reactive oxygen species (ROS) facilitated cell death, has provided an understanding of mechanisms that may determine the varied response to the histone deacetylase inhibitor. We found striking differences among these cancer cells in constitutive expression and response to suberoylanilide hydroxamic acid in levels of antiapoptotic and proapoptotic proteins, mitochondria membrane integrity, activation of caspases, ROS accumulation, and expression of thioredoxin, the major scavenger of ROS. Identifying these differences can have predictive value in assessing therapeutic response and identifying targets to enhance therapeutic efficacy. © 2006 by The National Academy of Sciences of the USA.
Keywords: controlled study; unclassified drug; human cell; histone deacetylase inhibitor; drug efficacy; antineoplastic agents; cell death; apoptosis; enzyme inhibition; neoplasm proteins; caspase; caspases; cell line, tumor; prediction; prostate cancer; prostatic neoplasms; cancer inhibition; intracellular signaling peptides and proteins; carrier proteins; vorinostat; hydroxamic acids; reactive oxygen species; reactive oxygen metabolite; mitochondrial membrane; mitochondria; histone deacetylases; protein inhibitor; enzyme mechanism; mitochondrial proteins; microtubule-associated proteins; suberoylanilide hydroxamic acid; thioredoxin; scavenger; membrane structure; x linked inhibitor of apoptosis; x-linked inhibitor of apoptosis protein; mitochondria membrane; thioredoxin-binding protein; 2 amino 6 bromo 4 (1 cyano 2 ethoxy 2 oxoethyl) 4h chromene 3 carboxylic acid ethyl ester; rmt 5256
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 103
Issue: 42
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 2006-10-17
Start Page: 15540
End Page: 15545
Language: English
DOI: 10.1073/pnas.0607518103
PUBMED: 17030815
PROVIDER: scopus
PMCID: PMC1592530
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-33750288048&partnerID=40&md5=da18db5e9cd7990fdc9f69fa1a1e9294
Notes: --- - "Cited By (since 1996): 77" - "Export Date: 4 June 2012" - "CODEN: PNASA" - "Source: Scopus"
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MSK Authors
  1. Milos Dokmanovic
    8 Dokmanovic
  2. Weisheng Xu
    13 Xu
  3. Lang Ngo
    27 Ngo
  4. Gisela Venta-Perez
    23 Venta-Perez
  5. Paul Marks
    186 Marks
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