TY - JOUR
T1 - Zinc-doped copper oxide nanocomposites inhibit the growth of human cancer cells through reactive oxygen species-mediated NF-κB activations
AU - Yuan, Ru
AU - Xu, Huanli
AU - Liu, Xiaohui
AU - Tian, Ye
AU - Li, Cong
AU - Chen, Xiaoliang
AU - Su, Shuonan
AU - Perelshtein, Ilana
AU - Gedanken, Aharon
AU - Lin, Xiukun
N1 - Publisher Copyright:
© 2016 American Chemical Society.
PY - 2016/11/23
Y1 - 2016/11/23
N2 - 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.
AB - 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.
KW - NF-κB activation
KW - antitumor mechanisms
KW - apoptosis
KW - cancer cell
KW - reactive oxygen species
KW - zinc-doped copper oxide nanocomposite
UR - http://www.scopus.com/inward/record.url?scp=84999208630&partnerID=8YFLogxK
U2 - 10.1021/acsami.6b09542
DO - 10.1021/acsami.6b09542
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C2 - 27791350
AN - SCOPUS:84999208630
SN - 1944-8244
VL - 8
SP - 31806
EP - 31812
JO - ACS Applied Materials and Interfaces
JF - ACS Applied Materials and Interfaces
IS - 46
ER -