PT - JOURNAL ARTICLE AU - JOON KI KIM AU - KYOUNG AH KANG AU - YEA SEONG RYU AU - MEI JING PIAO AU - XIA HAN AU - MIN CHANG OH AU - SUN JIN BOO AU - SEUNG UK JEONG AU - YONG JOO JEONG AU - SUNGWOOK CHAE AU - SOO-YOUNG NA AU - JIN WON HYUN TI - Induction of Endoplasmic Reticulum Stress <em>via</em> Reactive Oxygen Species Mediated by Luteolin in Melanoma Cells DP - 2016 May 01 TA - Anticancer Research PG - 2281--2289 VI - 36 IP - 5 4099 - http://ar.iiarjournals.org/content/36/5/2281.short 4100 - http://ar.iiarjournals.org/content/36/5/2281.full SO - Anticancer Res2016 May 01; 36 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.