title: 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.affiliation: Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan, R.O.C.
authors.forename: Shu-Fen
authors.initials: SF
authors.lastname: Peng
authors.forename: Chao-Ying
authors.initials: CY
authors.lastname: Lee
authors.forename: Mann-Jen
authors.initials: MJ
authors.lastname: Hour
authors.forename: Shih-Chang
authors.initials: SC
authors.lastname: Tsai
authors.forename: Daih-Huang
authors.initials: DH
authors.lastname: Kuo
authors.forename: Fu-An
authors.initials: FA
authors.lastname: Chen
authors.forename: Po-Chuen
authors.initials: PC
authors.lastname: Shieh
authors.forename: Jai-Sing
authors.initials: JS
authors.lastname: Yang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D051058:Oncogene Protein v-akt / Q000235:genetics* / Q000378:metabolism; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051025:bcl-Associated Death Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: C494819:BAD protein, human; D017382:Reactive Oxygen Species; D051025:bcl-Associated Death Protein; D051058:Oncogene Protein v-akt; D003474:Curcumin