title: Waltonitone induces apoptosis through mir-663-induced Bcl-2 downregulation in non-small cell lung cancer.
abstract: Our previous study reported that waltonitone treatment inhibited proliferation and induced apoptosis of lung cancer cells. However, the mechanism of waltonitone-induced toxicity remains unclear. In the present study, we treated H460 and H3255 lung cancer cells using different concentration of waltonitone (0, 10, 20, 30 μmol/L). We observed that waltonitone inhibited cell viability and induced apoptosis in a concentration dependent manner, with upregulation of caspase-3 cleavage. We also observed upregulation of miR-663, a potential tumor suppressor, after waltonitone treatment. Suppression of miR-663 function using miR-663 inhibitor partly alleviated cell toxicity induced by waltonitone. In addition, both waltonitone treatment and transfection of miR-663 mimic upregulated Bcl-2 mRNA and protein expression. Bcl-2 transfection alleviated waltonitone-induced toxicity. Furthermore, transfection of miR-663 inhibitor upregulated Bcl-2 levels in both cell lines. In summary, the present study demonstrated that waltonitone induced apoptosis of lung cancer cells through, at least partly, miR-663-induced Bcl-2 downregulation.
authors.affiliation: Department of Geriatrics, Shengjing Hospital of China Medical University, 36 Sanhao Road, Shenyang, 110004, China, cmuzhangyi@126.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhou
authors.forename: Xiaoman
authors.initials: X
authors.lastname: Xu
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Xue
authors.initials: X
authors.lastname: Bai
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Liang
authors.initials: L
authors.lastname: Kan
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhou
authors.forename: Huiyan
authors.initials: H
authors.lastname: Niu
authors.forename: Ping
authors.initials: P
authors.lastname: He
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D014315:Triterpenes / Q000008:administration & dosage*
chemical_list: C576118:28-hydroxy-3-oxo-12-ursene; C552243:MIRN663 microRNA, human; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; D014315:Triterpenes; D053148:Caspase 3