Abstract
BackgroundOsteosarcoma 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.MethodsThe 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.ResultsMG-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.ConclusionsThus, RACC-incorporated glycol chitosan nanoparticle strategy can be promising for the treatment of osteosarcoma.
Highlights
Osteosarcoma is the most common of all the bone malignancies and accounts for 30-80 % of the primary skeletal sarcomas
retinoic acid chlorochalcone (RACC)-incorporated glycol chitosan (GC) nanoparticles cause proliferation inhibition in human osteosarcoma cells The results from MTT assay revealed a dose-dependent inhibition of the MG-63 and Saos-2 cell proliferation on RACC treatment after 24 h
The results clearly showed that increase in concentration of RACC in RACC-incorporated GC nanoparticle from 10 μM to 25 μM significantly reduced the mitochondrial membrane potential in MG-63 cells (Fig. 5a)
Summary
Osteosarcoma is the most common of all the bone malignancies and accounts for 30-80 % of the primary skeletal sarcomas [1, 2]. It frequently attacks the children, teenagers, and young adults between 10–30 years of age [3]. Compared to females osteosarcoma is more predominantly observed in males. The long cylindrical bones like femur, tibia, and humerus including the knee joint are the main target in osteosarcomas [4].
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