Improvement and enhancement of antibladder carcinoma cell effects of heteronemin by the nanosized hyaluronan aggregation

Han Hsiang Huang,1 Shyh Ming Kuo,2 Yi-Jhen Wu,2 Jui-Hsin Su3 1Department of Veterinary Medicine, National Chiayi University, Chiayi City, 2Department of Biomedical Engineering, I-Shou University, Kaohsiung City, 3National Museum of Marine Biology and Aquarium, Pingtung, Taiwan Abstract: The effect...

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Autores principales:	Huang HH, Kuo SM, Wu YJ, Su JH
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	heteronemin hyaluronan chitosan nanoparticle bladder carcinoma cells Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/bd0035a9d9e640f6aa0370fab26fbe35
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spelling	oai:doaj.org-article:bd0035a9d9e640f6aa0370fab26fbe352021-12-02T05:04:30ZImprovement and enhancement of antibladder carcinoma cell effects of heteronemin by the nanosized hyaluronan aggregation1178-2013https://doaj.org/article/bd0035a9d9e640f6aa0370fab26fbe352016-03-01T00:00:00Zhttps://www.dovepress.com/improvement-and-enhancement-of-antibladder-carcinoma-cell-effects-of-h-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Han Hsiang Huang,1 Shyh Ming Kuo,2 Yi-Jhen Wu,2 Jui-Hsin Su3 1Department of Veterinary Medicine, National Chiayi University, Chiayi City, 2Department of Biomedical Engineering, I-Shou University, Kaohsiung City, 3National Museum of Marine Biology and Aquarium, Pingtung, Taiwan Abstract: The effects against tumors exerted by marine active compounds have been highlighted and investigated. Polymeric nanoparticles made from biodegradable and biocompatible molecules such as hyaluronan (HA) and chitosan (CHI) are able to aggregate the compounds to enhance their activities against tumor cells and reduce the toxicity on normal cells. Here, we extensively examined the antitumor activities and the mechanisms of HA/CHI nanoparticles-aggregated heteronemin (HET) extracted from the sponge Hippospongia sp. The half-maximal inhibitory concentration (IC50) of pure HET toward T24 bladder carcinoma cells is ~0.28 µg/mL. Pure HET from 0.2 to 0.8 µg/mL and HA nanoparticles-aggregated HET at 0.1 and 0.2 µg/mL significantly reduced T24 cell viability. Compared to pure HET, HA nanoparticles/HET aggregates showed much weaker viability-inhibitory effects on L929 normal fibroblasts. HET dose-dependently suppressed cancer cell migration as HA/CHI nanoparticles-aggregated HET displayed stronger migration-inhibitory effects than pure HET. Flow cytometric analysis showed that pure HET increased early/total apoptosis and JC-1 monomer fluorescence, while HA/CHI nanoparticles-aggregated HET induced higher apoptosis and JC-1 monomer rates than pure HET, suggesting that aggregation of HA nanoparticles offers HET stronger apoptosis-inducing capacity through mitochondrial depolarization. Western blot analysis showed that HA nanoparticles-aggregated HET further increased mitochondrial-associated, caspase-dependent and caspase-independent, as well as endoplasmic reticulum stress-related factors in comparison with pure HET. These data indicated that pure HET possesses cytotoxic, antimigratory, and apoptosis-inducing effects on bladder cancer cells in vitro, and its induction of apoptosis in bladder carcinoma cells is mainly caspase dependent. Moreover, HA nanoparticle aggregation reinforced the cytotoxic, antimigratory, and apoptosis-inducing activities against bladder carcinoma cells and attenuated the viability-inhibitory effects on normal fibroblasts. This aggregation reinforces antibladder carcinoma effects of HET via diverse routes, including mitochondrial-related/caspase-dependent, caspase-independent, and endoplasmic reticulum stress-related pathways. The current data also strongly suggested that HA/CHI nanoparticles-aggregated HET would be a potential treatment for urothelial cancer in vivo. Keywords: heteronemin, hyaluronan, chitosan, nanoparticle, bladder carcinoma cellsHuang HHKuo SMWu YJSu JHDove Medical Pressarticleheteroneminhyaluronanchitosannanoparticlebladder carcinoma cellsMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss default, Pp 1237-1251 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	heteronemin hyaluronan chitosan nanoparticle bladder carcinoma cells Medicine (General) R5-920
spellingShingle	heteronemin hyaluronan chitosan nanoparticle bladder carcinoma cells Medicine (General) R5-920 Huang HH Kuo SM Wu YJ Su JH Improvement and enhancement of antibladder carcinoma cell effects of heteronemin by the nanosized hyaluronan aggregation
description	Han Hsiang Huang,1 Shyh Ming Kuo,2 Yi-Jhen Wu,2 Jui-Hsin Su3 1Department of Veterinary Medicine, National Chiayi University, Chiayi City, 2Department of Biomedical Engineering, I-Shou University, Kaohsiung City, 3National Museum of Marine Biology and Aquarium, Pingtung, Taiwan Abstract: The effects against tumors exerted by marine active compounds have been highlighted and investigated. Polymeric nanoparticles made from biodegradable and biocompatible molecules such as hyaluronan (HA) and chitosan (CHI) are able to aggregate the compounds to enhance their activities against tumor cells and reduce the toxicity on normal cells. Here, we extensively examined the antitumor activities and the mechanisms of HA/CHI nanoparticles-aggregated heteronemin (HET) extracted from the sponge Hippospongia sp. The half-maximal inhibitory concentration (IC50) of pure HET toward T24 bladder carcinoma cells is ~0.28 µg/mL. Pure HET from 0.2 to 0.8 µg/mL and HA nanoparticles-aggregated HET at 0.1 and 0.2 µg/mL significantly reduced T24 cell viability. Compared to pure HET, HA nanoparticles/HET aggregates showed much weaker viability-inhibitory effects on L929 normal fibroblasts. HET dose-dependently suppressed cancer cell migration as HA/CHI nanoparticles-aggregated HET displayed stronger migration-inhibitory effects than pure HET. Flow cytometric analysis showed that pure HET increased early/total apoptosis and JC-1 monomer fluorescence, while HA/CHI nanoparticles-aggregated HET induced higher apoptosis and JC-1 monomer rates than pure HET, suggesting that aggregation of HA nanoparticles offers HET stronger apoptosis-inducing capacity through mitochondrial depolarization. Western blot analysis showed that HA nanoparticles-aggregated HET further increased mitochondrial-associated, caspase-dependent and caspase-independent, as well as endoplasmic reticulum stress-related factors in comparison with pure HET. These data indicated that pure HET possesses cytotoxic, antimigratory, and apoptosis-inducing effects on bladder cancer cells in vitro, and its induction of apoptosis in bladder carcinoma cells is mainly caspase dependent. Moreover, HA nanoparticle aggregation reinforced the cytotoxic, antimigratory, and apoptosis-inducing activities against bladder carcinoma cells and attenuated the viability-inhibitory effects on normal fibroblasts. This aggregation reinforces antibladder carcinoma effects of HET via diverse routes, including mitochondrial-related/caspase-dependent, caspase-independent, and endoplasmic reticulum stress-related pathways. The current data also strongly suggested that HA/CHI nanoparticles-aggregated HET would be a potential treatment for urothelial cancer in vivo. Keywords: heteronemin, hyaluronan, chitosan, nanoparticle, bladder carcinoma cells
format	article
author	Huang HH Kuo SM Wu YJ Su JH
author_facet	Huang HH Kuo SM Wu YJ Su JH
author_sort	Huang HH
title	Improvement and enhancement of antibladder carcinoma cell effects of heteronemin by the nanosized hyaluronan aggregation
title_short	Improvement and enhancement of antibladder carcinoma cell effects of heteronemin by the nanosized hyaluronan aggregation
title_full	Improvement and enhancement of antibladder carcinoma cell effects of heteronemin by the nanosized hyaluronan aggregation
title_fullStr	Improvement and enhancement of antibladder carcinoma cell effects of heteronemin by the nanosized hyaluronan aggregation
title_full_unstemmed	Improvement and enhancement of antibladder carcinoma cell effects of heteronemin by the nanosized hyaluronan aggregation
title_sort	improvement and enhancement of antibladder carcinoma cell effects of heteronemin by the nanosized hyaluronan aggregation
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/bd0035a9d9e640f6aa0370fab26fbe35
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Improvement and enhancement of antibladder carcinoma cell effects of heteronemin by the nanosized hyaluronan aggregation

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