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In this study, we investigated the antitumor activity of icariin (ICA) in human esophageal squamous cell carcinoma (ESCC) in vitro and in vivo and explored the role of endoplasmic reticulum stress (ERS) signaling in this activity. ICA treatment resulted in a dose- and time-dependent decrease in the viability of human EC109 and TE1 ESCCs. Additionally, ICA exhibited strong antitumor activity, as evidenced by reductions in cell migration, adhesion, and intracellular glutathione (GSH) levels and by increases in the EC109 and TE1 cell apoptotic index, Caspase 9 activity, reactive oxygen species (ROS) level, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. Furthermore, ICA treatments upregulated the levels of ERS-related molecules (p-PERK, GRP78, ATF4, p-eIF2α, and CHOP) and a pro-apoptotic protein (PUMA) and simultaneously downregulated an anti-apoptotic protein (Bcl2) in the two ESCC cell lines. The downregulation of ERS signaling using eIF2α siRNA desensitized EC109 and TE1 cells to ICA treatment, and the upregulation of ERS signaling using thapsigargin sensitized EC109 and TE1 cells to ICA treatment. In summary, ERS activation may represent a mechanism of action for the anticancer activity of ICA in ESCCs, and the activation of ERS signaling may represent a novel therapeutic intervention for human esophageal cancer.

Titel:	Icariin displays anticancer activity against human esophageal cancer cells via regulating endoplasmic reticulum stress-mediated apoptotic signaling.
Autor/in / Beteiligte Person:	Fan, C ; Yang, Y ; Liu, Y ; Jiang, S ; Di, S ; Hu, W ; Ma, Z ; Li, T ; Zhu, Y ; Xin, Z ; Wu, G ; Han, J ; Li, X ; Yan, X
Link:	Zum Volltext
Zeitschrift:	Scientific reports, Jg. 6 (2016-02-19), S. 21145
Veröffentlichung:	London : Nature Publishing Group, copyright 2011-, 2016
Medientyp:	academicJournal
ISSN:	2045-2322 (electronic)
DOI:	10.1038/srep21145
Schlagwort:	Animals Caspase 9 metabolism Cell Adhesion drug effects Cell Line, Tumor Cell Movement drug effects Cell Survival drug effects Disease Models, Animal Drugs, Chinese Herbal pharmacology Endoplasmic Reticulum Chaperone BiP Esophageal Neoplasms drug therapy Esophageal Neoplasms genetics Esophageal Neoplasms metabolism Esophageal Neoplasms pathology Eukaryotic Initiation Factor-2 genetics Eukaryotic Initiation Factor-2 metabolism Glutathione metabolism Humans Male Mice NADP metabolism Proto-Oncogene Proteins c-bcl-2 metabolism RNA, Small Interfering genetics Reactive Oxygen Species metabolism Xenograft Model Antitumor Assays Antineoplastic Agents, Phytogenic pharmacology Apoptosis drug effects Endoplasmic Reticulum Stress drug effects Flavonoids pharmacology Signal Transduction drug effects
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [Sci Rep] 2016 Feb 19; Vol. 6, pp. 21145. <i>Date of Electronic Publication: </i>2016 Feb 19. MeSH Terms: Antineoplastic Agents, Phytogenic / pharmacology ; Apoptosis / drug effects ; Endoplasmic Reticulum Stress / drug effects ; Flavonoids / pharmacology ; Signal Transduction / *drug effects ; Animals ; Caspase 9 / metabolism ; Cell Adhesion / drug effects ; Cell Line, Tumor ; Cell Movement / drug effects ; Cell Survival / drug effects ; Disease Models, Animal ; Drugs, Chinese Herbal / pharmacology ; Endoplasmic Reticulum Chaperone BiP ; Esophageal Neoplasms / drug therapy ; Esophageal Neoplasms / genetics ; Esophageal Neoplasms / metabolism ; Esophageal Neoplasms / pathology ; Eukaryotic Initiation Factor-2 / genetics ; Eukaryotic Initiation Factor-2 / metabolism ; Glutathione / metabolism ; Humans ; Male ; Mice ; NADP / metabolism ; Proto-Oncogene Proteins c-bcl-2 / metabolism ; RNA, Small Interfering / genetics ; Reactive Oxygen Species / metabolism ; Xenograft Model Antitumor Assays References: J Cell Biochem. 2011 Dec;112(12):3834-44. 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(PMID: 23629646) Substance Nomenclature: 0 (Antineoplastic Agents, Phytogenic) ; 0 (Drugs, Chinese Herbal) ; 0 (Endoplasmic Reticulum Chaperone BiP) ; 0 (Eukaryotic Initiation Factor-2) ; 0 (Flavonoids) ; 0 (HSPA5 protein, human) ; 0 (Hspa5 protein, mouse) ; 0 (Proto-Oncogene Proteins c-bcl-2) ; 0 (RNA, Small Interfering) ; 0 (Reactive Oxygen Species) ; 53-59-8 (NADP) ; EC 3.4.22.- (Caspase 9) ; GAN16C9B8O (Glutathione) ; VNM47R2QSQ (icariin) Entry Date(s): Date Created: 20160220 Date Completed: 20161219 Latest Revision: 20211203 Update Code: 20231215 PubMed Central ID: PMC4759694

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Icariin displays anticancer activity against human esophageal cancer cells via regulating endoplasmic reticulum stress-mediated apoptotic signaling.