Sanguinarine inhibits epithelial ovarian cancer development via regulating long non-coding RNA CASC2-EIF4A3 axis and/or inhibiting NF-κB signaling or PI3K/AKT/mTOR pathway

• Published in: Biomedicine & pharmacotherapy Vol. 102; pp. 302 - 308
• Main Authors: Zhang, Suxian, Leng, Tianyan, Zhang, Qin, Zhao, Qinghua, Nie, Xiaofeng, Yang, Lihua
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.06.2018
• Subjects: Apoptosis - drug effects; Benzophenanthridines - pharmacology; Carcinoma, Ovarian Epithelial; Cell Line, Tumor; Cell Movement - drug effects; Cell Proliferation - drug effects; DEAD-box RNA Helicases - genetics; EIF4A3; Eukaryotic Initiation Factor-4A - genetics; Female; Gene Expression Regulation, Neoplastic - drug effects; Humans; Isoquinolines - pharmacology; Long non-coding RNA CASC2; Neoplasms, Glandular and Epithelial - genetics; Neoplasms, Glandular and Epithelial - metabolism; Neoplasms, Glandular and Epithelial - pathology; Neoplasms, Glandular and Epithelial - prevention & control; NF-kappa B - antagonists & inhibitors; Nuclear factor-κB signaling; Ovarian cancer; Ovarian Neoplasms - genetics; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Ovarian Neoplasms - prevention & control; Phosphatidylinositol 3-Kinases - metabolism; PI3K/AKT/mTOR pathway; Protein Binding; Proto-Oncogene Proteins c-akt - metabolism; RNA, Long Noncoding - genetics; Sanguinarine; Signal Transduction; TOR Serine-Threonine Kinases - metabolism; Tumor Suppressor Proteins - genetics; Long non-coding RNA CASC2; PI3K/AKT/mTOR pathway; Sanguinarine; Nuclear factor-κB signaling; EIF4A3; Ovarian cancer
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2018.03.071

This study aimed to investigate the antitumor effects and possible regulatory mechanisms of sanguinarine in epithelial ovarian cancer. The effects of sanguinarine on the malignant behaviors of epithelial ovarian cancer SKOV3 cells and the expression of long non-coding RNA CASC2 were investigated. The expression of CASC2 and EIF4A3 in epithelial ovarian cancer tissues and cells were detected, and the potential mechanisms of sanguinarine were explored by investigating the interactions between CASC2 and EIF4A3. Furthermore, the regulatory relationship between sanguinarine and nuclear factor-κB (NF-κB) signaling or PI3K/AKT/mTOR pathway was explored. Sanguinarine exhibited antitumor effects in SKOV3 cells by significantly inhibiting cell viability, migration and invasion and promoting cell apoptosis. Moreover, sanguinarine induced CASC2 expression and silencing of CASC2 reversed the effects of sanguinarine in epithelial ovarian cancer cells. CASC2 was significantly lowly expressed in ovarian cancer tissues and cells, while EIF4A3 was highly expressed. EIF4A3 was identified as a CASC2 binding protein. Knockdown of EIF4A3 reversed the effects of sanguinarine plus CASC2 silencing. Besides, sanguinarine markedly inhibited the activation of NF-κB signaling or PI3K/AKT/mTOR pathway, which was reversed by CASC2 silencing. And the effects of sanguinarine plus CASC2 silencing on the activation of these pathways were further reversed after knockdown of EIF4A3 at the same time. Our findings reveal that sanguinarine exhibits antitumor effects in epithelial ovarian cancer cells possible via regulating CASC2-EIF4A3 axis and/or inhibiting NF-κB signaling or PI3K/AKT/mTOR pathway. Sanguinarine may serve as a potential therapeutic reagent for epithelial ovarian cancer.