Antitumor activity of vorinostat-incorporated nanoparticles against human cholangiocarcinoma cells View Full Text


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Article Info

DATE

2015-09-26

AUTHORS

Tae Won Kwak, Do Hyung Kim, Young-Il Jeong, Dae Hwan Kang

ABSTRACT

BackgroundThe aim of this study is to evaluate the anticancer activity of vorinostat-incorporated nanoparticles (vorinostat-NPs) against HuCC-T1 human cholangiocarcinoma cells. Vorinostat-NPs were fabricated by a nanoprecipitation method using poly(dl-lactide-co-glycolide)/poly(ethylene glycol) copolymer.ResultsVorinostat-NPs exhibited spherical shapes with sizes <100 nm. Vorinostat-NPs have anticancer activity similar to that of vorinostat in vitro. Vorinostat-NPs as well as vorinostat itself increased acetylation of histone-H3. Furthermore, vorinostat-NPs have similar effectiveness in the suppression or expression of histone deacetylase, mutant type p53, p21, and PARP/cleaved caspase-3. However, vorinostat-NPs showed improved antitumor activity against HuCC-T1 cancer cell-bearing mice compared to vorinostat, whereas empty nanoparticles had no effect on tumor growth. Furthermore, vorinostat-NPs increased the expression of acetylated histone H3 in tumor tissue and suppressed histone deacetylase (HDAC) expression in vivo. The improved antitumor activity of vorinostat-NPs can be explained by molecular imaging studies using near-infrared (NIR) dye-incorporated nanoparticles, i.e. NIR-dye-incorporated nanoparticles were intensively accumulated in the tumor region rather than normal one.ConclusionsOur results demonstrate that vorinostat and vorinostat-NPs exert anticancer activity against HuCC-T1 cholangiocarcinoma cells by specific inhibition of HDAC expression. Thus, we suggest that vorinostat-NPs are a promising candidate for anticancer chemotherapy in cholangiocarcinoma.Graphical abstractLocal delivery strategy of vorinostat-NPs against cholangiocarcinomas. More... »

PAGES

60

References to SciGraph publications

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  • 2006-12-12. Cancer biology: mechanism of antitumour action of vorinostat (suberoylanilide hydroxamic acid), a novel histone deacetylase inhibitor in BRITISH JOURNAL OF CANCER
  • 2011-07-13. Down-Regulated Expression of HSP70 in Correlation with Clinicopathology of Cholangiocarcinoma in PATHOLOGY & ONCOLOGY RESEARCH
  • 2012-01-20. SAHA Inhibits the Growth of Colon Tumors by Decreasing Histone Deacetylase and the Expression of Cyclin D1 and Survivin in PATHOLOGY & ONCOLOGY RESEARCH
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    http://scigraph.springernature.com/pub.10.1186/s12951-015-0122-4

    DOI

    http://dx.doi.org/10.1186/s12951-015-0122-4

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1009018247

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/26410576


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