In:
Oxidative Medicine and Cellular Longevity, Hindawi Limited, Vol. 2017 ( 2017), p. 1-13
Abstract:
Breast cancer is characterized by overexpression of superoxide dismutase (SOD) and downregulation of catalase and more resistance to hydrogen peroxide (H 2 O 2 ) than normal cells. Thus, relatively high H 2 O 2 promotes breast cancer cell growth and proliferation. However, excessive intracellular H 2 O 2 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 H 2 O 2 . In the present study, we demonstrated that triethylenetetramine (TETA) enhances Asc autoxidation and thus elevates H 2 O 2 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 H 2 O 2 -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 H 2 O 2 overproduction in breast cancer cells, which suppresses RAS/ERK pathway and results in apoptosis.
Type of Medium:
Online Resource
ISSN:
1942-0900
,
1942-0994
DOI:
10.1155/2017/3481710
Language:
English
Publisher:
Hindawi Limited
Publication Date:
2017
detail.hit.zdb_id:
2455981-7
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