Cycling hypoxia up-regulates thioredoxin levels in human MDA-MB-231 breast cancer cells

Biochemical and Biophysical Research Communications
Therese C KarleniusKathryn F Tonissen

Abstract

The thioredoxin system is a key cellular antioxidant system and is highly expressed in cancer cells, especially in more aggressive and therapeutic resistant tumors. We analysed the expression of the thioredoxin system in the MDA-MB-231 breast cancer cell line under conditions mimicking the tumor oxygen microenvironment. We grew breast cancer cells in either prolonged hypoxia or hypoxia followed by various lengths of reoxygenation and in each case cells were cultured with or without a hypoxic cycling preconditioning (PC) phase preceding the hypoxic growth. Flow cytometry-based assays were used to measure reactive oxygen species (ROS) levels. Cells grown in hypoxia showed a significant decrease in ROS levels compared to normoxic cells, while a significant increase in ROS levels over normoxic cells was observed after 4 h of reoxygenation. The PC pre-treatment did not have a significant effect on ROS levels. Thioredoxin levels were also highest after 4 h of reoxygenation, however cells subjected to PC pre-treatment displayed even higher thioredoxin levels. The high level of intracellular thioredoxin was also reflected on the cell surface. Reporter assays showed that activity of the thioredoxin and thioredoxin reductase gene promote...Continue Reading

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Citations

Dec 30, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Bo Ra YouWoo Hyun Park
Aug 29, 2016·European Journal of Cell Biology·Maneet BhatiaKathryn F Tonissen
Oct 28, 2016·Apoptosis : an International Journal on Programmed Cell Death·Prahlad V RaningaKathryn F Tonissen
Jan 24, 2019·Cancers·Hui WangMark De Ridder
May 16, 2019·International Journal of Cancer. Journal International Du Cancer·Prahlad V RaningaKum Kum Khanna
May 7, 2015·Oncotarget·Prahlad V RaningaKathryn F Tonissen
Oct 3, 2018·Biological & Pharmaceutical Bulletin·Xiao LiuMingyong Han

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