Glycol chitosan incorporated retinoic acid chlorochalcone (RACC) nanoparticles in the treatment of Osteosarcoma.

Abstract

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 IC50 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.

• Authors: Yan-Guo Qin, Lan-Yu Zhu, Chen-Yu Wang, Bo-Yan Zhang, Qing-Yu Wang, Rui-Yan Li, Zhen Liu
• Journal: Lipids in health and disease (Lipids Health Dis) Vol. 14 Pg. 70 (Jul 14 2015) ISSN: 1476-511X [Electronic] England
• PMID: 26170203 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Retracted Publication)

Chemical References

• Cyclohexanones
• glycol-chitosan
• retinoic acid chlorochalcone
• Tretinoin
• Chitosan
• EZH2 protein, human
• Enhancer of Zeste Homolog 2 Protein
• Polycomb Repressive Complex 2
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Apoptosis (drug effects)
• Cell Cycle Checkpoints (drug effects)
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Chitosan (chemistry)
• Cyclohexanones (chemistry, therapeutic use)
• Enhancer of Zeste Homolog 2 Protein
• Humans
• Male
• Mice
• Mitochondria (drug effects, metabolism)
• Nanoparticles (chemistry)
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Osteosarcoma (drug therapy, pathology)
• Phosphorylation (drug effects)
• Polycomb Repressive Complex 2 (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Time Factors
• Transfection
• Tretinoin (analogs & derivatives, chemistry, therapeutic use)