Efficacy on anaplastic thyroid carcinoma of valproic acid alone or in combination with doxorubicin, a synthetic chenodeoxycholic acid derivative, or lactacystin

  • Authors: Tae Hyun Kim, Young Hyun Yoo, Do-Young Kang, Hongsuk Suh, Moon Ki Park, Ki-Jae Park, Sung-Heun Kim
  • View Affiliations

  • Published online on: Friday, May 1, 2009
  • Pages: 1353-1362
  • DOI: 10.3892/ijo_00000262

Abstract

The present study investigated the mechanism underlying the antitumor activity of the histone deacetylases inhibitor valproic acid (VPA), alone and in combination with doxorubicin, a synthetic chenodeoxycholic acid derivative (HS-1200), or the proteasome inhibitor lactacystin on cultured anaplastic thyroid carcinoma KAT-18 cells. Cell viability was evaluated by trypan-blue exclusion. Western blotting determined caspase and histone deacetylase activities and expression of poly(ADP)-ribose polymerase. Induction of apoptosis was identified by Hoechst staining, DNA electrophoresis, DNA hypoploidy and cell cycle phase analysis, and measurement of mitochondrial membrane potential. Subcellular translocation of apoptosis inducing factor and caspase-activated DNase after treatment was determined by confocal microscopy following immunofluorescent staining. VPA treatment increased apoptotic death of KAT-18 cells. VPA treatment was also associated with degradation of procaspase-3, procaspase-7, and poly(ADP)-ribose polymerase; induction of histone hyperacetylation; condensation of peripheral chromatin; decreased mitochondrial membrane potential and DNA content; and decreased translocation of apoptosis inducing factor and caspase-activated DNase. VPA in combination with doxorubicin, HS-1200, or lactacystin, applied at the highest concentrations that did not induce KAT-18 cell death, efficiently induced apoptosis in KAT-18 cells. The results suggest VPA combination therapy may represent an alternative therapeutic strategy for anaplastic thyroid carcinoma.
Journal Cover

May 2009
Volume 34 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

2012 Impact Factor: 2.657
Ranked #31/196 Oncology
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APA
Kim, T., Yoo, Y., Kang, D., Suh, H., Park, M., Park, K., & Kim, S. (2009). Efficacy on anaplastic thyroid carcinoma of valproic acid alone or in combination with doxorubicin, a synthetic chenodeoxycholic acid derivative, or lactacystin. International Journal of Oncology, 34(5), 1353-1362.
MLA
Kim, Yoo, Kang, Suh, Park, Park, and Sung-Heun Kim. "Efficacy on anaplastic thyroid carcinoma of valproic acid alone or in combination with doxorubicin, a synthetic chenodeoxycholic acid derivative, or lactacystin." International Journal of Oncology International Journal of Oncology 34.5 (2009): 1353-1362.
Chicago
Kim, Yoo, Kang, Suh, Park, Park, and Sung-Heun Kim. "Efficacy on anaplastic thyroid carcinoma of valproic acid alone or in combination with doxorubicin, a synthetic chenodeoxycholic acid derivative, or lactacystin." International Journal of Oncology International Journal of Oncology 34 no. 5 (2009): 1353-1362.