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Glycol chitosan incorporated retinoic acid chlorochalcone (RACC) nanoparticles in the treatment of Osteosarcoma
BACKGROUND: Osteosarcoma is the most common of all the bone malignancies and accounts for 30-80 % of the primary skeletal sarcomas. The overall survival rate of patients with osteosarcoma is < 20 % suggesting poor prognosis. METHODS: The present study demonstrates the effect of retinoic acid chlo...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4501080/ https://www.ncbi.nlm.nih.gov/pubmed/26170203 http://dx.doi.org/10.1186/s12944-015-0068-4 |
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author | Qin, Yan-Guo Zhu, Lan-Yu Wang, Chen-Yu Zhang, Bo-Yan Wang, Qing-Yu Li, Rui-Yan Liu, Zhen |
author_facet | Qin, Yan-Guo Zhu, Lan-Yu Wang, Chen-Yu Zhang, Bo-Yan Wang, Qing-Yu Li, Rui-Yan Liu, Zhen |
author_sort | Qin, Yan-Guo |
collection | PubMed |
description | BACKGROUND: Osteosarcoma is the most common of all the bone malignancies and accounts for 30-80 % of the primary skeletal sarcomas. The overall survival rate of patients with osteosarcoma is < 20 % suggesting poor prognosis. METHODS: The present study demonstrates the effect of retinoic acid chlorochalcone (RACC) incorporated glycol chitosan (GC) nanoparticle transfection in osteosarcoma cells. MG-63 and Saos-2 osteosarcoma cells were transfected with various concentrations of RACC-incorporated GC nanoparticle for 24 h. The effect on cell proliferation, Ezh2 expression, apoptosis, cell cycle arrest, cell migration and invasiveness, Akt phosphorylation and local tumour growth and metastases were studied. RESULTS: MG-63 and Saos-2 osteosarcoma cells on RACC-incorporated GC nanoparticle transfection for 24 h showed a concentration-dependent inhibition of cell proliferation. Of the various concentrations of RACC tested, the effective concentration started from 5 μM with an IC(50) of 20 μM. Wound healing assay also showed that RACC-incorporated GC nanoparticles inhibited migration of tumor cells more effectively compared to the parent RA. RACC transfection resulted in inhibition of cell proliferation, Ezh2 expression inhibition, apoptosis through mitochondrial pathway by decrease in membrane potential and release of cytochrome c and cell cycle arrest in the G0/G1 phase. The invasiveness of cells treated with 5 and 20 μM RACC was decreased by 49 and 76 % respectively, compared to the control. RACC-treated mice showed significantly lower number of metastases compared to that in the control mice. CONCLUSIONS: Thus, RACC-incorporated glycol chitosan nanoparticle strategy can be promising for the treatment of osteosarcoma. |
format | Online Article Text |
id | pubmed-4501080 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-45010802015-07-15 Glycol chitosan incorporated retinoic acid chlorochalcone (RACC) nanoparticles in the treatment of Osteosarcoma Qin, Yan-Guo Zhu, Lan-Yu Wang, Chen-Yu Zhang, Bo-Yan Wang, Qing-Yu Li, Rui-Yan Liu, Zhen Lipids Health Dis Research BACKGROUND: Osteosarcoma is the most common of all the bone malignancies and accounts for 30-80 % of the primary skeletal sarcomas. The overall survival rate of patients with osteosarcoma is < 20 % suggesting poor prognosis. METHODS: The present study demonstrates the effect of retinoic acid chlorochalcone (RACC) incorporated glycol chitosan (GC) nanoparticle transfection in osteosarcoma cells. MG-63 and Saos-2 osteosarcoma cells were transfected with various concentrations of RACC-incorporated GC nanoparticle for 24 h. The effect on cell proliferation, Ezh2 expression, apoptosis, cell cycle arrest, cell migration and invasiveness, Akt phosphorylation and local tumour growth and metastases were studied. RESULTS: MG-63 and Saos-2 osteosarcoma cells on RACC-incorporated GC nanoparticle transfection for 24 h showed a concentration-dependent inhibition of cell proliferation. Of the various concentrations of RACC tested, the effective concentration started from 5 μM with an IC(50) of 20 μM. Wound healing assay also showed that RACC-incorporated GC nanoparticles inhibited migration of tumor cells more effectively compared to the parent RA. RACC transfection resulted in inhibition of cell proliferation, Ezh2 expression inhibition, apoptosis through mitochondrial pathway by decrease in membrane potential and release of cytochrome c and cell cycle arrest in the G0/G1 phase. The invasiveness of cells treated with 5 and 20 μM RACC was decreased by 49 and 76 % respectively, compared to the control. RACC-treated mice showed significantly lower number of metastases compared to that in the control mice. CONCLUSIONS: Thus, RACC-incorporated glycol chitosan nanoparticle strategy can be promising for the treatment of osteosarcoma. BioMed Central 2015-07-14 /pmc/articles/PMC4501080/ /pubmed/26170203 http://dx.doi.org/10.1186/s12944-015-0068-4 Text en © Qin et al. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Qin, Yan-Guo Zhu, Lan-Yu Wang, Chen-Yu Zhang, Bo-Yan Wang, Qing-Yu Li, Rui-Yan Liu, Zhen Glycol chitosan incorporated retinoic acid chlorochalcone (RACC) nanoparticles in the treatment of Osteosarcoma |
title | Glycol chitosan incorporated retinoic acid chlorochalcone (RACC) nanoparticles in the treatment of Osteosarcoma |
title_full | Glycol chitosan incorporated retinoic acid chlorochalcone (RACC) nanoparticles in the treatment of Osteosarcoma |
title_fullStr | Glycol chitosan incorporated retinoic acid chlorochalcone (RACC) nanoparticles in the treatment of Osteosarcoma |
title_full_unstemmed | Glycol chitosan incorporated retinoic acid chlorochalcone (RACC) nanoparticles in the treatment of Osteosarcoma |
title_short | Glycol chitosan incorporated retinoic acid chlorochalcone (RACC) nanoparticles in the treatment of Osteosarcoma |
title_sort | glycol chitosan incorporated retinoic acid chlorochalcone (racc) nanoparticles in the treatment of osteosarcoma |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4501080/ https://www.ncbi.nlm.nih.gov/pubmed/26170203 http://dx.doi.org/10.1186/s12944-015-0068-4 |
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