Curcumin-loaded nanoparticles enhance apoptotic cell death of U2OS human osteosarcoma cells through the Akt-Bad signaling pathway.

Abstract

Curcumin has potential anticancer activity and has been shown to be involved in several signaling pathways including differentiation and apoptosis. Our previous study showed that water-soluble PLGA curcumin nanoparticles (Cur-NPs) triggered apoptotic cell death through regulation of the function of MDR1 and the production of reactive oxygen species (ROS) in cisplatin-resistant human oral cancer CAR cells. In this study, we investigated the anti-proliferative effects of Cur-NPs on human osteosarcoma U2OS cells. The morphology of Cur-NPs showed spherical shape by TEM analysis. The encapsulation efficiency of curcumin in Cur-NPs prepared by single emulsion was 90.5 ± 3.0%. Our results demonstrated that the curcumin fragments on the mass spectrum of Cur-NPs and the peaks of curcumin standard could be found on the Cur-NPs spectrum by 1H-NMR spectra analysis. Cur-NPs induced anti-proliferative effects and apoptosis in U2OS cells. Compared to the untreated U2OS cells, more detectable amount of Cur-NPs was found inside the treated U2OS cells. Cur-NPs induced DNA fragmentation and apoptotic bodies in U2OS cells. Both the activity and the expression levels of caspases-3/-7 and caspase-9 were elevated in the treated U2OS cells. Cur-NPs upregulated the protein expression levels of cleaved caspase-3/caspase-9, cytochrome c, Apaf-1 and Bad and downregulated the protein expression level of p-Akt in U2OS cells. These results suggest Cur-NPs are effective in enhancing apoptosis in human osteosarcoma cells and thus could provide potential for cancer therapeutics.

• Authors: Shu-Fen Peng, Chao-Ying Lee, Mann-Jen Hour, Shih-Chang Tsai, Daih-Huang Kuo, Fu-An Chen, Po-Chuen Shieh, Jai-Sing Yang
• Journal: International journal of oncology (Int J Oncol) Vol. 44 Issue 1 Pg. 238-46 (Jan 2014) ISSN: 1791-2423 [Electronic] Greece
• PMID: 24247158 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BAD protein, human
• Reactive Oxygen Species
• bcl-Associated Death Protein
• Oncogene Protein v-akt
• Curcumin

Topics

• Apoptosis (drug effects)
• Cell Line, Tumor
• Curcumin (administration & dosage, chemistry)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Nanoparticles (administration & dosage, chemistry)
• Oncogene Protein v-akt (genetics, metabolism)
• Osteosarcoma (drug therapy, genetics, pathology)
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects)
• bcl-Associated Death Protein (genetics, metabolism)