Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 8, Issue 46, Pages 31806-31812Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.6b09542
Keywords
zinc-doped copper oxide nanocomposite; cancer cell; antitumor mechanisms; apoptosis; reactive oxygen species; NF-kappa B activation
Funding
- National Innovative Drug Development Projects [2014ZX-09102043-001]
- 863 High Technology Project of China [2014AA093503]
- Natural Science Foundation of China [81302906, 81273550, 81573457, 41306157]
- Shandong Provincial Natural Science Foundation [ZR2014HQ031, ZR2015HQ027]
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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-IKK alpha/beta and nucleus p-NF-kappa B p65 expressions and decrease IKK alpha, IKK beta, I kappa B alpha, and nucleus NF-kappa B 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-kappa B activation. The current study provides primary evidence that nZn-CuO NPs possess the potential to be developed as a novel anticancer agent.
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