title: Activation of endoplasmic reticulum stress is involved in the activity of icariin against human lung adenocarcinoma cells.
abstract: In this study, we investigated the anticancer activity of icariin (ICA) against human lung adenocarcinoma cells in vitro and in vivo and explored the role of endoplasmic reticulum (ER) stress (ERS) signaling in this process. ICA treatment resulted in a dose- and time-dependent decrease in the viability of human lung adenocarcinoma A549 cells. Additionally, ICA exhibited potent anticancer activity, as evidenced by reductions in A549 cell adhesion, migration and intracellular glutathione (GSH) levels and increases in the apoptotic index, Caspase 3 activity, and reactive oxygen species. Furthermore, ICA treatment increased the expression of ERS-related molecules (p-PERK, ATF6, GRP78, p-eIF2α, and CHOP), up-regulated the apoptosis-related protein PUMA and down-regulated the anti-apoptosis-related protein Bcl2. The down-regulation of ERS signaling using PERK siRNA desensitized lung adenocarcinoma cells to ICA treatment, whereas the up-regulation of ERS signaling using thapsigargin (THA) sensitized lung adenocarcinoma cells to ICA treatment. Additionally, ICA inhibited the growth of human lung adenocarcinoma A549 cell xenografts by increasing the expression of ERS-related molecules (p-PERK and CHOP), up-regulating PUMA, and down-regulating Bcl2. These data indicate that ICA is a potential inhibitor of lung adenocarcinoma cell growth by targeting ERS signaling and suggest that the activation of ERS signaling may represent a novel therapeutic intervention for lung adenocarcinoma.
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, 1 Xinsi Road, Xi'an, 710038, China.
authors.forename: Shouyin
authors.initials: S
authors.lastname: Di
authors.forename: Chongxi
authors.initials: C
authors.lastname: Fan
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Shuai
authors.initials: S
authors.lastname: Jiang
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Liang
authors.forename: Guiling
authors.initials: G
authors.lastname: Wu
authors.forename: Bodong
authors.initials: B
authors.lastname: Wang
authors.forename: Zhenlong
authors.initials: Z
authors.lastname: Xin
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.forename: Yifang
authors.initials: Y
authors.lastname: Zhu
authors.forename: Weimiao
authors.initials: W
authors.lastname: Li
authors.forename: Yongan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Li
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Yan
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D000077192:Adenocarcinoma of Lung; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D008819:Mice, Nude; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D004791:Enzyme Inhibitors; D005419:Flavonoids; C000717247:HSPA5 protein, human; C000717248:Hspa5 protein, mouse; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D019284:Thapsigargin; D053148:Caspase 3; D005978:Glutathione; C056599:icariin