title: Toosendanin inhibits growth and induces apoptosis in colorectal cancer cells through suppression of AKT/GSK-3β/β-catenin pathway.
abstract: AKT/GSK-3β/β-catenin signaling pathway plays an important role in the progression of colorectal cancer (CRC). Toosendanin (TSN) is a triterpenoid extracted from the bark or fruits of Melia toosendan Sieb et Zucc and possesses antitumour effects on various human cancer cells. However, its effect on CRC remains poorly understood. The present study investigated the effect of TSN on CRC SW480 cells and the AKT/GSK-3β/β-catenin signaling. Proliferation assay, flow cytometry and Hoechst 33342 nuclear staining demonstrated TSN dose-dependently inhibited cell viability and induced cell apoptosis as well as cell cycle arrest in S phase. Confocal laser scanning microscope showed β-catenin transferred to the outside of the nucleus in TSN-treated cells. Quantitative real-time PCR and western blot analysis found that TSN effectively modulated molecules related to apoptosis and AKT/GSK-3β/β-catenin signaling. Moreover, TSN administration significantly inhibited CRC growth in a mouse tumor xenograft model. In conclusion, our findings indicate that TSN inhibits growth and induces apoptosis in CRC cells through suppression of AKT/GSK-3β/β-catenin pathway, suggesting that TSN may have potential for use in CRC treatment.
authors.affiliation: Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.
authors.forename: Ge
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Medicine, Rudong Hospital of Traditional Chinese Medicine, Nantong, Jiangsu 226400, P.R. China.
authors.forename: Cheng-Cheng
authors.initials: CC
authors.lastname: Feng
authors.affiliation: Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.
authors.forename: Shao-Jun
authors.initials: SJ
authors.lastname: Chu
authors.affiliation: Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.
authors.forename: Yun-Min
authors.initials: YM
authors.lastname: Lu
authors.affiliation: Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.
authors.forename: Jin-Shui
authors.initials: JS
authors.lastname: Zhu
authors.affiliation: Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D051379:Mice; D051058:Oncogene Protein v-akt / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects; D051176:beta Catenin / Q000235:genetics*; D014315:Triterpenes
chemical_list: D004365:Drugs, Chinese Herbal; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D051058:Oncogene Protein v-akt; D051176:beta Catenin; C036454:toosendanin; D014315:Triterpenes; C000605506:GSK3B protein, human; C000605507:Gsk3b protein, mouse