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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2019.00333

Inhibition of murine breast cancer metastases by hydrophilic As4S4 nanoparticles is associated with decreased ROS and HIF-1α downregulation

 Tao Wang1,  Jie Meng1*, Chuan Wang1, Mengfan Jia1, Yangyang Ge1, Lifei Xie1, Suisui Hao1, Jian Liu1, Tao Wen1 and  Haiyan Xu1*
  • 1Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, China

As4S4 is a mineral drug that can be administrated orally and has been applied in the treatment of myeloid leukemia. The aim of this work is to investigate the therapeutic effect of As4S4 in highly metastatic triple-negative breast cancer animal model, as As4S4 has not been applied in the treatment of breast cancer yet. To overcome the poor solubility of original As4S4, a formulation of hydrophilic As4S4 nanoparticles (e-As4S4) developed previously was applied to mouse breast cancer cells as well as the tumor-bearing mice. It was shown that e-As4S4 was much more cytotoxic than r-As4S4, strongly inhibiting the proliferation of the cells and scavenging intracellular reactive oxygen species (ROS). The oral administration of e-As4S4 significantly increased the accumulation of arsenic in the tumor tissue and eliminated ROS in tumor tissues. Besides, e-As4S4 could also inhibit the activation of hypoxia-inducible factor-1α (HIF-1α) and NLRP3 inflammasomes. Consequently, the angiogenesis was reduced, the metastasis to lung and liver was inhibited and the survival of tumor-bearing mice was prolonged. In conclusion, e-As4S4 holds great potential for an alternative therapeutics in the treatment of breast cancer, due to its unique function of correcting the aggressive microenvironment.

Keywords: breast cancer, As4S4 nanoparticles, Reactive Oxygen Species, Hypoxic tumor microenvironment, Inflammation

Received: 09 Jan 2019; Accepted: 11 Apr 2019.

Edited by:

Lina Ghibelli, University of Rome Tor Vergata, Italy

Reviewed by:

Ivana Kurelac, University of Bologna, Italy
Fanny Caputo, CEA Grenoble, France  

Copyright: © 2019 Wang, Meng, Wang, Jia, Ge, Xie, Hao, Liu, Wen and Xu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Jie Meng, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100730, China, mengjie@ibms.pumc.edu.cn
Prof. Haiyan Xu, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100730, China, xuhy@pumc.edu.cn