RT Journal Article SR Electronic T1 Induction of Endoplasmic Reticulum Stress via Reactive Oxygen Species Mediated by Luteolin in Melanoma Cells JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 2281 OP 2289 VO 36 IS 5 A1 JOON KI KIM A1 KYOUNG AH KANG A1 YEA SEONG RYU A1 MEI JING PIAO A1 XIA HAN A1 MIN CHANG OH A1 SUN JIN BOO A1 SEUNG UK JEONG A1 YONG JOO JEONG A1 SUNGWOOK CHAE A1 SOO-YOUNG NA A1 JIN WON HYUN YR 2016 UL http://ar.iiarjournals.org/content/36/5/2281.abstract AB Background: This study aimed to investigate whether luteolin, a flavonoid, induces apoptosis in human melanoma cells via endoplasmic reticulum (ER) stress. Materials and Methods: To investigate the effects of luteolin in human melanoma cells, the anti-proliferation, apoptosis, ER stress induction and reactive oxygen species (ROS) generation were evaluated using MTT, Hoechst 33342, ER-tracker Blue White DPX and DCF-DA staining assays, respectively. Results: Luteolin inhibited cell proliferation and increased apoptotic body formation. Luteolin induced ER stress, as shown by ER staining and mitochondrial Ca2+ overloading. Luteolin increased expression of the ER stress-related proteins; protein kinase RNA-like ER kinase, phospho eukaryotic translation initiation factor 2α, activating transcription factor (ATF) 6, CCAAT/enhancer-binding protein-homologous protein (CHOP), and cleaved caspase 12. Furthermore, luteolin increased the level of intracellular ROS, leading to ROS-mediated apoptosis and ER stress. However, N-acetyl cysteine, a ROS scavenger, decreased ROS levels, apoptosis, and ER stress induced by luteolin treatment. In addition, knockdown of CHOP and ATF6 by small-interfering RNA inhibited luteolin-induced cell death. Conclusion: Luteolin induces apoptosis by ER stress via increasing ROS levels.