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

Citations Over TimeTop 10% of 2016 papers

Abstract

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.

Related Papers

• → Modeling Acute ER Stress in Vivo and in Vitro(2016)120 cited
• → Klotho Ameliorates Chemically Induced Endoplasmic Reticulum (ER) Stress Signaling(2013)49 cited
• → The regulatory mechanism of 4-phenylbutyric acid against ER stress-induced autophagy in human gingival fibroblasts(2012)46 cited
• ER Stress에 의해 유발된 C6 Glial Cells의 손상에 대한 龍腦의 보호효과(2009)
• Inhibition of CaMKII Suppresses the Endoplasmic Reticulum Stress-induced Cardiomyocytes Death in Rats(2009)