Retrochalcone Echinatin Triggers Apoptosis of Esophageal Squamous Cell Carcinoma via ROS- and ER Stress-Mediated Signaling Pathways

• Published in: Molecules (Basel, Switzerland) Switzerland), 2019-11, Vol.24 (22), p.4055
• Main Authors: Kwak, Ah-Won, Choi, Joon-Seok, Lee, Mee-Hyun, Oh, Ha-Na, Cho, Seung-Sik, Yoon, Goo, Liu, Kangdong, Chae, Jung-Il, Shim, Jung-Hyun
• Format: Article
• Language: English
• Subjects: Antitumor activity; Apoptosis; Apoptosis - genetics; Biomarkers, Tumor - metabolism; c-jun n-terminal kinase; Cdc2 protein; Cell cycle; Cell growth; Cell Line, Tumor; Cell Proliferation - drug effects; Chalcones - pharmacology; Cyclin B1; echinatin; Endoplasmic Reticulum Stress - drug effects; Esophageal cancer; Esophageal Neoplasms - drug therapy; Esophageal Neoplasms - metabolism; esophageal squamous cell carcinoma; Esophageal Squamous Cell Carcinoma - drug therapy; Esophageal Squamous Cell Carcinoma - metabolism; Esophagus; G2 Phase Cell Cycle Checkpoints - drug effects; GTP-binding protein; Herbal medicine; Humans; Inflammation; JNK Mitogen-Activated Protein Kinases - metabolism; Kinases; MAP kinase; MAP Kinase Signaling System - drug effects; p38; p38 Mitogen-Activated Protein Kinases - metabolism; Phosphorylation; Phosphorylation - drug effects; Proteins; reactive oxygen species; Reactive Oxygen Species - metabolism; Signal Transduction - drug effects; Squamous cell carcinoma; Stress; Stress proteins; Survival
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules24224055

Esophageal squamous cell carcinoma (ESCC) is a poor prognostic cancer with a low five-year survival rate. Echinatin (Ech) is a retrochalone from licorice. It has been used as a herbal medicine due to its anti-inflammatory and anti-oxidative effects. However, its anticancer activity or underlying mechanism has not been elucidated yet. Thus, the objective of this study was to investigate the anti-tumor activity of Ech on ESCC by inducing ROS and ER stress dependent apoptosis. Ech inhibited ESCC cell growth in anchorage-dependent and independent analysis. Treatment with Ech induced G2/M phase of cell cycle and apoptosis of ESCC cells. It also regulated their related protein markers including p21, p27, cyclin B1, and cdc2. Ech also led to phosphorylation of JNK and p38. Regarding ROS and ER stress formation associated with apoptosis, we found that Ech increased ROS production, whereas its increase was diminished by NAC treatment. In addition, ER stress proteins were induced by treatment with Ech. Moreover, Ech enhanced MMP dysfunction and caspases activity. Furthermore, it regulated related biomarkers. Taken together, our results suggest that Ech can induce apoptosis in human ESCC cells via ROS/ER stress generation and p38 MAPK/JNK activation.