title: Esculetin induces apoptosis in human colon cancer cells by inducing endoplasmic reticulum stress.
abstract: Colorectal cancer has become more common in many regions of the world. Recently, we showed that esculetin, a natural coumarin, induces apoptosis in HT-29 colon cancer cells via the reactive oxygen species-mediated mitochondrial pathway. The present study examined whether esculetin induces apoptosis in HT-29 colon cancer cells by inducing endoplasmic reticulum (ER) stress. We found that esculetin induced characteristic signs of ER stress, confirmed by ER staining, mitochondrial calcium overload and expression of ER stress-related proteins (i.e. glucose regulated protein 78, phosphorylated ribonucleic acid-dependent protein kinase-like ER kinase, phosphorylated inositol requiring enzyme 1, phosphorylated eukaryotic initiation factor-2α, spliced X-box binding protein 1 and cleaved activating transcription factor 6). Esculetin also induced the expression of the CCAAT/enhancer-binding protein-homologous protein (CHOP) and pro-apoptotic factors caspase-12. Moreover, transfection of colon cancer cells with a small interfering ribonucleic acid targeting CHOP attenuated esculetin-induced apoptosis. Taken together, these results suggest that the ER stress response plays an important role in esculetin-induced apoptosis in human colon cancer cells.
authors.affiliation: School of Medicine, Jeju National University, Jeju, Korea.
authors.forename: Areum Daseul
authors.initials: AD
authors.lastname: Kim
authors.affiliation: School of Medicine, Jeju National University, Jeju, Korea.
authors.forename: Susara Ruwan Kumara
authors.initials: SR
authors.lastname: Madduma Hewage
authors.affiliation: School of Medicine, Jeju National University, Jeju, Korea.
authors.forename: Mei Jing
authors.initials: MJ
authors.lastname: Piao
authors.affiliation: School of Medicine, Jeju National University, Jeju, Korea.
authors.forename: Kyoung Ah
authors.initials: KA
authors.lastname: Kang
authors.affiliation: School of Medicine, Jeju National University, Jeju, Korea.
authors.forename: Suk Ju
authors.initials: SJ
authors.lastname: Cho
authors.affiliation: School of Medicine, Jeju National University, Jeju, Korea.
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Hyun
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015179:Colorectal Neoplasms / Q000503:physiopathology; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D019073:HT29 Cells; D006801:Humans; D051742:Transcription Factor CHOP / Q000037:antagonists & inhibitors; D014468:Umbelliferones / Q000494:pharmacology*
chemical_list: C497249:DDIT3 protein, human; D016166:Free Radical Scavengers; D014468:Umbelliferones; D051742:Transcription Factor CHOP; C007628:esculetin
keywords: CCAAT/enhancer-binding protein homologous protein; apoptosis; colon cancer; endoplasmic reticulum stress; esculetin