title: Zinc-Doped Copper Oxide Nanocomposites Inhibit the Growth of Human Cancer Cells through Reactive Oxygen Species-Mediated NF-κB Activations.
abstract: Zinc-doped copper oxide nanocomposites (nZn-CuO NPs) are novel nanparticles synthesized by our group. In the present study, the antitumor effects and the underlying molecular mechanisms of the nZn-CuO NPs were investigated. The cytotoxicity of nZn-CuO NPs against several types of cancer cell lines was studied using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS)/phenazinemethosulfate (PMS) assay. Results showed that nZn-CuO NPs exerted obvious antiproliferation effects on cancer cells and relatively weak antiproliferation effects on normal cells. The antitumor mechanisms of nZn-CuO NPs were further investigated using human liver cancer HepG2 cells and human pancreatic cancer Panc28 cells. Hoechst 33342 staining and FITC-Annexin V/PI staining showed that nZn-CuO NPs could induce cell apoptosis in a dose dependent manner. Cell-cycle analysis using flow cytometry revealed that nZn-CuO NPs were able to arrest the cell cycle in the G2/M phase. Also, nZn-CuO NPs were found to induce reactive oxygen species (ROS) generation. Further studies confirmed that nZn-CuO NPs could increase p-IKKα/β and nucleus p-NF-κB p65 expressions and decrease IKKα, IKKβ, IκBα, and nucleus NF-κB p65 expressions in both cell lines. Overall, our data demonstrated that nZn-CuO NPs could selectively inhibit the growth of cancer cells via ROS-mediated NF-κB activation. The current study provides primary evidence that nZn-CuO NPs possess the potential to be developed as a novel anticancer agent.
authors: Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University , Beijing 100069, China.
authors: Ru
authors: R
authors: Yuan
authors: Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University , Beijing 100069, China.
authors: Huanli
authors: H
authors: Xu
authors: Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University , Beijing 100069, China.
authors: Xiaohui
authors: X
authors: Liu
authors: Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University , Beijing 100069, China.
authors: Ye
authors: Y
authors: Tian
authors: Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University , Beijing 100069, China.
authors: Cong
authors: C
authors: Li
authors: Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University , Beijing 100069, China.
authors: Xiaoliang
authors: X
authors: Chen
authors: Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University , Beijing 100069, China.
authors: Shuonan
authors: S
authors: Su
authors: Department of Chemistry and Nanomaterials, Bar-Ilan University Center for Advanced Materialsand Nanotechnology , Ramat-Gan 52900, Israel.
authors: Ilana
authors: I
authors: Perelshtein
authors: Department of Chemistry and Nanomaterials, Bar-Ilan University Center for Advanced Materialsand Nanotechnology , Ramat-Gan 52900, Israel.
authors: Aharon
authors: A
authors: Gedanken
authors: Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University , Beijing 100069, China.
authors: Xiukun
authors: X
authors: Lin
keywords: NF-κB activation; antitumor mechanisms; apoptosis; cancer cell; reactive oxygen species; zinc-doped copper oxide nanocomposite