TY - JOUR T1 - Hypoxia Suppresses Cysteine Deprivation-induced Cell Death <em>Via</em> ATF4 Regulation in MDA-MB-231 Breast Cancer Cells JF - Anticancer Research JO - Anticancer Res SP - 1387 LP - 1394 DO - 10.21873/anticanres.14080 VL - 40 IS - 3 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 Y1 - 2020/03/01 UR - http://ar.iiarjournals.org/content/40/3/1387.abstract N2 - 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. ER -