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Valproic acid causes dose- and time-dependent changes in nuclear structure in prostate cancer cellsin vitroandin vivo
- Source :
- Molecular Cancer Therapeutics. 8:802-808
- Publication Year :
- 2009
- Publisher :
- American Association for Cancer Research (AACR), 2009.
-
Abstract
- Histone deacetylase inhibitors such as valproic acid (VPA) are promising anticancer agents that change the acetylation status of histones and loosen the chromatin structure. We assessed nuclear structure changes induced by VPA in prostate cancer LNCaP, CWR22R, DU145, and PC3 cell lines and xenografts and their potential use as a biomarker of treatment. In vitro tissue microarrays consisted of prostate cancer cell lines treated for 3, 7, or 14 days with 0, 0.6, or 1.2 mmol/L VPA. In vivo tissue microarrays consisted of cores from prostate cancer xenografts from nude mice treated for 30 days with 0.2% or 0.4% VPA in drinking water. Digital images of at least 200 Feulgen DNA-stained nuclei were captured using the Nikon CoolScope and nuclear alterations were measured. With a set of seven most frequently significant nuclear alterations (determined by univariate logistic regression analysis), control and VPA treatment nuclei were compared in vitro and in vivo. Depending on the cell line, area under the curve-receiver operating characteristics ranged between 0.6 and 0.9 and were dose- and time-dependent both in vitro and in vivo. Also, VPA treatment caused significant nuclear alterations in normal drug-filtering organs (liver and kidney tissue). In vitro and in vivo VPA treatment of prostate cancer cell lines results in significant dose- and time-dependent changes in nuclear structure. Further, VPA induces nuclear structural changes in normal liver and kidney tissue, which likely reflects a natural physiologic response. Therefore, nuclear structural alterations may serve as a biomarker for histone deacetylase inhibitor treatment. [Mol Cancer Ther 2009;8(4):802–8]
- Subjects :
- Male
Cancer Research
Time Factors
medicine.drug_class
Mice, Nude
In Vitro Techniques
Pharmacology
Biology
Kidney
Article
Mice
Prostate cancer
DU145
In vivo
Cell Line, Tumor
LNCaP
medicine
Animals
Humans
Enzyme Inhibitors
Cell Nucleus
Tissue microarray
Dose-Response Relationship, Drug
Valproic Acid
Histone deacetylase inhibitor
Prostatic Neoplasms
DNA, Neoplasm
medicine.disease
Xenograft Model Antitumor Assays
Cell nucleus
medicine.anatomical_structure
Liver
Oncology
lipids (amino acids, peptides, and proteins)
Histone deacetylase
Subjects
Details
- ISSN :
- 15388514 and 15357163
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Molecular Cancer Therapeutics
- Accession number :
- edsair.doi.dedup.....061a043f1d00c9da164bad05d93db243