title: Trichosanthin suppresses the proliferation of glioma cells by inhibiting LGR5 expression and the Wnt/β-catenin signaling pathway.
abstract: Studies have indicated that trichosanthin (TCS), a bioactive protein extracted and purified from the tuberous root of Trichosanthes kirilowii (a well‑known traditional Chinese medicinal plant), produces antitumor effects on various types of cancer cells. However, the effects of TCS on glioma cells are poorly understood. The objective of this study was to investigate the antitumor effects of TCS on the U87 and U251 cell lines. The in vitro effects of TCS on these two cell lines were determined using a Cell Counting Kit‑8 (CCK‑8) assay, Annexin V‑FITC staining, DAPI staining, Transwell assays, terminal deoxynucleotidyl transferase‑mediated dUTP nick end‑labeling (TUNEL) assays, 5,5',6,6'‑tetrachloro‑1,1',3,3'‑tetraethyl‑imidacarbocyanine iodide (JC‑1) staining and western blotting, which was utilized to assess the expression of leucine‑rich repeat‑containing G protein‑coupled receptor 5 (LGR5) and key proteins in the Wnt/β‑catenin signaling pathway. Our data indicated that TCS inhibited the proliferation of glioma cells in a dose‑ and time‑dependent manner and played a role in inhibiting glioma cell invasion and migration. Additional investigation revealed that the expression levels of LGR5 and of key proteins in the Wnt/β‑catenin signaling pathway were markedly decreased after TCS treatment. The results suggest that TCS may induce apoptosis in glioma cells by targeting LGR5 and repressing the Wnt/β‑catenin signaling pathway. In the future, in vivo experiments should be conducted to examine the potential use of this compound as a novel therapeutic agent for gliomas.
authors.affiliation: Department of Neurosurgery, Peking University People's Hospital, Beijing 100044, P.R. China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Miao
authors.affiliation: Department of Neurosurgery, Peking University People's Hospital, Beijing 100044, P.R. China.
authors.forename: Yilin
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Neurosurgery, Peking University People's Hospital, Beijing 100044, P.R. China.
authors.forename: Dongliang
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Peking University People's Hospital, Beijing 100044, P.R. China.
authors.forename: Jingru
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery, Peking University People's Hospital, Beijing 100044, P.R. China.
authors.forename: Cungang
authors.initials: C
authors.lastname: Fan
authors.affiliation: Department of Neurosurgery, Peking University People's Hospital, Beijing 100044, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Jiao
authors.affiliation: Department of Neurosurgery, Peking University People's Hospital, Beijing 100044, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Peking University People's Hospital, Beijing 100044, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Peking University People's Hospital, Beijing 100044, P.R. China.
authors.forename: Yangshuo
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Peking University People's Hospital, Beijing 100044, P.R. China.
authors.forename: Qingjun
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage* / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis* / Q000235:genetics; D029778:Trichosanthes / Q000737:chemistry; D015978:Trichosanthin / Q000008:administration & dosage* / Q000737:chemistry; D060449:Wnt Signaling Pathway / Q000187:drug effects
chemical_list: D004365:Drugs, Chinese Herbal; C116884:LGR5 protein, human; D043562:Receptors, G-Protein-Coupled; D015978:Trichosanthin