scholarly journals Thymidine phosphorylase enhances reactive oxygen species generation and interleukin-8 expression in human cancer cells

2012 ◽  
Author(s):  
Shin-Ichi Akiyama
Keyword(s):  
Reactive Oxygen Species ◽  
Cancer Cells ◽  
Thymidine Phosphorylase ◽  
Human Cancer ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Interleukin 8 ◽  
Oxygen Species ◽  
Human Cancer Cells

scholarly journals The Anticancer Drug 3-Bromopyruvate Induces DNA Damage Potentially Through Reactive Oxygen Species in Yeast and in Human Cancer Cells

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1161 ◽  
Author(s):  
Magdalena Cal ◽  
Irwin Matyjaszczyk ◽  
Ireneusz Litwin ◽  
Daria Augustyniak ◽  
Rafał Ogórek ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Dna Damage ◽  
Cancer Cells ◽  
Human Cancer ◽  
Reactive Oxygen ◽  
Atp Depletion ◽  
Mitochondrial Enzymes ◽  
Oxygen Species ◽  
Human Cancer Cells ◽  
The Impact

3-bromopyruvate (3-BP) is a small molecule with anticancer and antimicrobial activities. 3-BP is taken up selectively by cancer cells’ mono-carboxylate transporters (MCTs), which are highly overexpressed by many cancers. When 3-BP enters cancer cells it inactivates several glycolytic and mitochondrial enzymes, leading to ATP depletion and the generation of reactive oxygen species. While mechanisms of 3-BP uptake and its influence on cell metabolism are well understood, the impact of 3-BP at certain concentrations on DNA integrity has never been investigated in detail. Here we have collected several lines of evidence suggesting that 3-BP induces DNA damage probably as a result of ROS generation, in both yeast and human cancer cells, when its concentration is sufficiently low and most cells are still viable. We also demonstrate that in yeast 3-BP treatment leads to generation of DNA double-strand breaks only in S-phase of the cell cycle, possibly as a result of oxidative DNA damage. This leads to DNA damage, checkpoint activation and focal accumulation of the DNA response proteins. Interestingly, in human cancer cells exposure to 3-BP also induces DNA breaks that trigger H2A.X phosphorylation. Our current data shed new light on the mechanisms by which a sufficiently low concentration of 3-BP can induce cytotoxicity at the DNA level, a finding that might be important for the future design of anticancer therapies.

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