Antitumor activity of vorinostat-incorporated nanoparticles against human cholangiocarcinoma cells.

Abstract

BACKGROUND:

The 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.

RESULTS:

Vorinostat-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.

CONCLUSIONS:

Our 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 abstract Local delivery strategy of vorinostat-NPs against cholangiocarcinomas.

• Authors: Tae Won Kwak, Do Hyung Kim, Young-Il Jeong, Dae Hwan Kang
• Journal: Journal of nanobiotechnology (J Nanobiotechnology) Vol. 13 Pg. 60 (09 26 2015) ISSN: 1477-3155 [Electronic] England
• PMID: 26410576 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Hydroxamic Acids
• Vorinostat

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Blotting, Western
• Cell Line, Tumor
• Cholangiocarcinoma (drug therapy, pathology)
• Fluorescence
• Humans
• Hydroxamic Acids (pharmacology, therapeutic use)
• Immunohistochemistry
• Mice
• Nanoparticles (chemistry, ultrastructure)
• Particle Size
• Vorinostat
• X-Ray Diffraction
• Xenograft Model Antitumor Assays