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Tropical Journal of Pharmaceutical Research
Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, Nigeria
ISSN: 1596-5996 EISSN: 1596-5996
Vol. 14, No. 9, 2015, pp. 1581-1588
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Bioline Code: pr15206
Full paper language: English
Document type: Research Article
Document available free of charge
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Tropical Journal of Pharmaceutical Research, Vol. 14, No. 9, 2015, pp. 1581-1588
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Role of Glycol Chitosan-incorporated Ursolic Acid Nanoparticles in the Treatment of Osteosarcoma
Zhang, Xing-Lin; Lu, Xing; Geng, Wei; Qu, Gao-Wei; Zhou, Zhi-Yong; Jiang, Lian-Hong; Li, Yun-Xiang; Chen, Xu & Lin-Nie
Abstract
Purpose: To investigate the effect of ursolic acid (UA)-incorporated glycol chitosan (GC) nanoparticles
on inhibition of human osteosarcoma.
Methods: U2OS and Saos-2 osteosarcoma cells were transfected with ursolic acid (UA) incorporated
glycol chitosan (GC) nanoparticles. Ultraviolet (UV) spectrophotometry was used to measure drug
contents in nanoparticles at 365 nm with empty GC vehicles as blank. Bicinchoninic acid assay (BCA)
method was employed to determine protein concentration. Identification of apoptosis and necrosis in
osteosarcoma cells was performed by propidium iodide and FITC-annexin V reagents, respectively.
FAC Scan flow cytometry was used to analyse apoptotic cells.
Results: Among the range of UA concentrations tested, the minimum effective concentration was 10
μM with half inhibitory concentration IC50 of 25 μM. In U2OS cells, treatment with 10 and 25 μM UA-induced
apoptosis in 5.89 ± 3.90 and 60.54 ± 5.40 % cells, respectively, compared to 2.05 ± 1.01 %
cells for control. In Saos-2 cells, exposure to 10 and 25 μM UA induced apoptosis in 9.86 ± 8.89 and
47.54 ± 14.5 % cells, respectively, compared to 1.79 ± 0.23 % for control cells. Western blot analysis
revealed translocation of Bax and Bcl-2 proteins from mitochondria to cell cytosol. Increase in UA
concentration from 10 μM to 25 μM led to increase in the proportion of cells in G0/G1 phase and
decrease in the number of cells in S and G2/M phases. These results confirm that UA transfection
arrests cell cycle in G0/G1 phase in human osteosarcoma cell lines.
Conclusion: UA transfection resulted in the inhibition of cell proliferation, Ezh2 expression inhibition,
and apoptosis via mitochondrial pathway due to decrease in membrane potential and release of
cytochrome C, as well as cell cycle arrest in G0/G1 phase.
Keywords
Osteosarcoma; Cell cycle arrest; Palliation; Glycol chitosan; Ursolic acid
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