RT Journal Article SR Electronic T1 Hypoxia Suppresses Cysteine Deprivation-induced Cell Death Via ATF4 Regulation in MDA-MB-231 Breast Cancer Cells JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 1387 OP 1394 DO 10.21873/anticanres.14080 VO 40 IS 3 A1 SUNG-EUN HONG A1 MI-RI KIM A1 SE-KYEONG JANG A1 MIN-KI SEONG A1 HYUN-AH KIM A1 WOO CHUL NOH A1 HYEON-OK JIN A1 IN-CHUL PARK YR 2020 UL http://ar.iiarjournals.org/content/40/3/1387.abstract 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.