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Oxidative Medicine and Cellular Longevity
Volume 2017 (2017), Article ID 3481710, 13 pages
https://doi.org/10.1155/2017/3481710
Research Article

Triethylenetetramine Synergizes with Pharmacologic Ascorbic Acid in Hydrogen Peroxide Mediated Selective Toxicity to Breast Cancer Cell

1Department of Reproduction Health and Infertility, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
2Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
3Canada-China-New Zealand Joint Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing 400016, China
4Molecular Medicine and Cancer Research Center, Department of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016, China
5College of Medicine, University of Leicester, Leicester LE1 7RH, UK
6Laboratory of Lipid & Glucose Metabolism, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
7Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Chongqing 400016, China

Correspondence should be addressed to Chao Tong; moc.361@umqcgnotoahc

Received 12 October 2016; Accepted 5 January 2017; Published 8 February 2017

Academic Editor: Lynne Postovit

Copyright © 2017 Lianlian Wang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Breast cancer is characterized by overexpression of superoxide dismutase (SOD) and downregulation of catalase and more resistance to hydrogen peroxide (H2O2) than normal cells. Thus, relatively high H2O2 promotes breast cancer cell growth and proliferation. However, excessive intracellular H2O2 leads to death of breast cancer cells. In cancer cells, high level ascorbic acid (Asc) is able to be autoxidized and thus provides an electron to oxygen to generate H2O2. In the present study, we demonstrated that triethylenetetramine (TETA) enhances Asc autoxidation and thus elevates H2O2 production in MCF-7 cells. Furthermore, Asc/TETA combination significantly impaired cancer cell viability, while having much milder effects on normal cells, indicating Asc/TETA could be a promising therapy for breast cancer. Moreover, SOD1 and N-acetyl-L-cysteine failed to improve MCF-7 cells viability in the presence of Asc/TETA, while catalase significantly inhibited the cytotoxicity of Asc/TETA to breast cancer cells, strongly suggesting that the selective cytotoxicity of Asc/TETA to cancer cells is H2O2-dependent. In addition, Asc/TETA induces RAS/ERK downregulation in breast cancer cells. Animal studies confirmed that Asc/TETA effectively suppressed tumor growth in vivo. In conclusion, TETA synergizes pharmacologic Asc autoxidation and H2O2 overproduction in breast cancer cells, which suppresses RAS/ERK pathway and results in apoptosis.