PT  - JOURNAL ARTICLE
AU  - SUNG-EUN HONG
AU  - MI-RI KIM
AU  - SE-KYEONG JANG
AU  - MIN-KI SEONG
AU  - HYUN-AH KIM
AU  - WOO CHUL NOH
AU  - HYEON-OK JIN
AU  - IN-CHUL PARK
TI  - Hypoxia Suppresses Cysteine Deprivation-induced Cell Death <em>Via</em> ATF4 Regulation in MDA-MB-231 Breast Cancer Cells
AID  - 10.21873/anticanres.14080
DP  - 2020 Mar 01
TA  - Anticancer Research
PG  - 1387--1394
VI  - 40
IP  - 3
4099  - http://ar.iiarjournals.org/content/40/3/1387.short
4100  - http://ar.iiarjournals.org/content/40/3/1387.full
SO  - Anticancer Res2020 Mar 01; 40
AB  - Background/Aim: Cancer cells are frequently exposed to microenvironmental stresses, including amino acid deprivation and hypoxia, which are often targeted for cancer therapy. Here, we examined the effect of hypoxia in cysteine-deprived breast cancer cells and the mechanism to counteract the hypoxia effect. Materials and Methods: Cell death was determined by annexin V-FITC and propidium iodide staining. Expression of mRNAs and proteins was determined by reverse transcription polymerase chain reaction and western blot analysis, respectively. Results: Cysteine deprivation or sulfasalazine, a potent inhibitor of cysteine/glutamate transporter, induced cell death by activating transcription factor 4 (ATF4) up-regulation. Hypoxia significantly suppressed cell death and ATF4 up-regulation induced by cysteine deprived conditions. In addition, tumor necrosis factor-related apoptosis-inducing ligand reversed the effect of hypoxia on cysteine deprived conditions. Conclusion: Prevention of hypoxia may be a means for augmenting the effect of amino acid deprivation as a strategy for cancer therapy.