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Zn‐doped CuO nanocomposites inhibit tumor growth in vitro and in vivo : Involvement of reactive oxygen species‐dependent autophagy and apoptosis cross‐linked by NF‐kappaB pathway
Author(s) -
Xu Huanli,
Yuan Ru,
Liu Xiaohui,
Gedanken Aharon,
Lin Xiukun
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.811.7
Subject(s) - pyrrolidine dithiocarbamate , autophagy , reactive oxygen species , apoptosis , chemistry , western blot , in vivo , microbiology and biotechnology , programmed cell death , biochemistry , nf κb , biology , gene
Zn‐doped CuO nanocomposites (Zn‐CuO NPs) are novel nanoparticles synthesized by sonochemical method. This study aimed to investigate the in vitro and in vivo antitumor effects and mechanism of Zn‐CuO NPs, as well as the exact roles of reactive oxygen species (ROS) in Zn‐CuO NPs‐induced cell death using N ‐acetylcysteine, an ROS scavenger. The antitumor effects of Zn‐CuO NPs were evaluated by 3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐ (4‐sulfophenyl)‐2H‐tetrazolium assay and orthotopic transplantation tumor model in nude mice. The effects of Zn‐CuO NPs with or without N ‐acetylcysteine on ROS production, DNA damage, apoptosis, mitochondrial damage, autophagy, lysosome impairment, and endoplasmic reticulum and Golgi stress were determined. Western blot was used to detect apoptosis and autophagy related proteins, as well as NF‐κB pathway related proteins. Also, the effects of NF‐κB pathway inhibitor, pyrrolidine dithiocarbamate, on Zn‐CuO NPs induced apoptosis and autophagy were detected. Zn‐CuO NPs significantly inhibit tumor growth both in vitro and in vivo . Zn‐CuO NPs were able to cause cytotoxicity, ROS production, DNA damage mitochondrial damage, apoptosis, and autophagy. ROS scavenger N ‐acetylcysteine attenuated all of the above effects induced by Zn‐CuO NPs in cancer cells. Western blot analysis revealed that N ‐acetylcysteine also restored the effects of Zn‐CuO NPs on protein expressions related to apoptosis, autophagy, and NF‐κB pathways. NF‐κB pathway inhibitor pyrrolidine dithiocarbamate significantly attenuated Zn‐CuO NPs induced apoptosis and autophagy. Overall, our data demonstrated that Zn‐CuO NPs could inhibit tumor growth both in vitro and in vivo by ROS‐dependent regulation of apoptosis and autophagy, which might be cross‐linked by NF‐κB pathways. Support or Funding Information The study was supported by the Natural Science Foundation of China (# 81773776, 81573457, and 81774191), the Beijing Natural Science Foundation (#7172031 and 7172029).Graphic Abstract for this ManuscriptThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .