Open AccessCombination of Disulfiram and Copper–Cysteamine Nanoparticles for an Enhanced Antitumor Effect on Esophageal Cancer
Author(s) -
Yan Chang,
Fang Wu,
Nil Kanatha Pandey,
Lalit Chudal,
Meiying Xing,
Xiaoli Zhang,
Nguyen Linh-Trung,
Xian Liu,
J Ping Liu,
Wei Chen,
Zui Pan
Publication year - 2020
Publication title -
acs applied bio materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.764
H-Index - 17
ISSN - 2576-6422
DOI - 10.1021/acsabm.0c00949
Subject(s) - disulfiram , chemistry , esophageal cancer , pharmacology , cancer cell , apoptosis , cysteamine , cancer research , cancer , toxicity , medicine , biochemistry , organic chemistry
Esophageal cancer (EC) is the sixth leading cause of cancer deaths worldwide with a low 5-year survival rate. More effective chemotherapeutic drugs, either new or repurposing ones, are urgently needed. Disulfiram (DSF) is a safe and public domain drug for alcohol addiction treatment and later shown to have anti-cancer capability, especially when administrated together with copper. The present study is to test the hypothesis that a newly developed copper-cysteamine (Cu-Cy) nanoparticles (NPs) can enhance the anti-tumor effect of DSF on esophageal cancer with reduced risk of copper poisoning. Our results showed that Cu-Cy NPs could greatly facilitate DSF to inhibit cell proliferation in cultured human esophageal cancer cells. Interestingly, the combined inhibitory function could be further enhanced when DSF and Cu-Cy NPs were present at an optimal molar ratio of 1:4. The results of the change in physical color, UV-vis absorption and fluorescence spectra, X-ray diffraction patterns, and FTIR spectra from a mixture of DSF and Cu-Cy NPs suggest a possible reaction between DSF and Cu-Cy NPs and the formation of new materials. Furthermore, cellular mechanistic studies revealed that the combination of DSF and Cu-Cy NPs resulted in reactive oxygen species (ROS) accumulation, and blocked nuclear translocation of NF-ƙB (p65) in esophageal cancer cells. Moreover, in xenograft nude mice, combined administration of DSF and Cu-Cy NPs greatly inhibited tumor growth without noticeable histological toxicity, while any single agent at the same doses presented no inhibitory function. Together, this study demonstrates an effective anti-cancer function of combined treatment of DSF and Cu-Cy NPs in vitro and in vivo, which could be a promising new chemotherapy for esophageal cancer patients.