Induction of Endoplasmic Reticulum Stress via Reactive Oxygen Species Mediated by Luteolin in Melanoma Cells.

Abstract

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 Ca(2+) 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.

• Authors: Joon Ki Kim, Kyoung Ah Kang, Yea Seong Ryu, Mei Jing Piao, Xia Han, Min Chang Oh, Sun Jin Boo, Seung Uk Jeong, Yong Joo Jeong, Sungwook Chae, Soo-Young Na, Jin Won Hyun
• Journal: Anticancer research (Anticancer Res) Vol. 36 Issue 5 Pg. 2281-9 (May 2016) ISSN: 1791-7530 [Electronic] Greece
• PMID: 27127134 (Publication Type: Journal Article)
• Copyright: Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Chemical References

• ATF6 protein, human
• Activating Transcription Factor 6
• DDIT3 protein, human
• Neoplasm Proteins
• RNA, Small Interfering
• Reactive Oxygen Species
• Transcription Factor CHOP
• Luteolin
• Calcium

Topics

• Activating Transcription Factor 6 (antagonists & inhibitors, genetics)
• Apoptosis (drug effects)
• Calcium (analysis)
• Cell Line, Tumor
• Endoplasmic Reticulum Stress (drug effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Luteolin (pharmacology)
• Melanoma (pathology)
• Mitochondria (chemistry, drug effects)
• Neoplasm Proteins (antagonists & inhibitors, biosynthesis, genetics)
• RNA, Small Interfering (genetics)
• Reactive Oxygen Species
• Staining and Labeling
• Transcription Factor CHOP (antagonists & inhibitors, genetics)
• Transfection
• Tumor Stem Cell Assay