title: Fatsioside A inhibits the growth of glioma cells via the induction of endoplasmic reticulum stress-mediated apoptosis.
abstract: Malignant gliomas are a common type of primary tumor of the central nervous system. In spite of current intensive therapy, the prognosis of patients with malignant glioma remains poor, hence the development of novel therapeutic modalities is necessary. Cell apoptosis is a frequent target in the development of anti‑cancer drugs. Fatsioside A, a novel baccharane‑type triterpenoid glycoside, is extracted from the fruits of Fatsia japonica. Previous studies have shown that Fatsioside A induces growth inhibition, cell cycle arrest and apoptosis in C6 rat glioma cells and U251 human glioma cells. However, to the best of our knowledge, no detailed studies have reported its effect on U87MG glioma cells and its exact mechanisms remain unknown. In the current study, the growth inhibitory effect of Fatsioside A on U87MG cells was evaluated and the underlying molecular mechanisms were explored. Through the use of flow cytometry and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, it was determined that Fatsioside A markedly inhibits the growth of U87MG cells. Mechanistic studies demonstrated that Fatsioside A induces growth inhibition of U87MG cells via the induction of endoplasmic reticulum (ER) stress, which was supported by the upregulation of ER stress markers, including elevated levels of phosphorylation of PERK and eIF2α, the increased expression levels of CHOP and the accelerated cleavage of caspase‑4. The downregulation of CHOP via CHOP‑specific siRNA reduced the growth‑inhibitive effect of Fatsioside A on U87MG cells, further confirming the role of the ER stress response in mediating Fatsioside A‑induced growth inhibition. In conclusion, Fatsioside A inhibits glioma cell growth via the induction of ER stress‑mediated apoptosis. This may provide a molecular basis for the development of Fatsioside A into a drug candidate for the treatment of malignant glioma.
authors.affiliation: Department of Neurosurgery, Yantaishan Hospital, Yantai, Shandong 264000, P.R. China.
authors.forename: Ji-Ming
authors.initials: JM
authors.lastname: Pan
authors.affiliation: Clinical Laboratory, Yantai Hospital of Traditional Chinese Medicine, Yantai, Shandong 264000, P.R. China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery, Yantaishan Hospital, Yantai, Shandong 264000, P.R. China.
authors.forename: Guang-Bin
authors.initials: GB
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Yantaishan Hospital, Yantai, Shandong 264000, P.R. China.
authors.forename: Guang-Wen
authors.initials: GW
authors.lastname: Xia
authors.affiliation: Department of Neurosurgery, Yantaishan Hospital, Yantai, Shandong 264000, P.R. China.
authors.forename: Kun
authors.initials: K
authors.lastname: Xue
authors.affiliation: Department of Neurosurgery, Yantaishan Hospital, Yantai, Shandong 264000, P.R. China.
authors.forename: Xin-Guo
authors.initials: XG
authors.lastname: Cui
authors.affiliation: Department of Neurosurgery, Yantaishan Hospital, Yantai, Shandong 264000, P.R. China.
authors.forename: Hong-Zhi
authors.initials: HZ
authors.lastname: Shi
authors.affiliation: Department of Neurosurgery, Yantaishan Hospital, Yantai, Shandong 264000, P.R. China.
authors.forename: Jian-Hui
authors.initials: JH
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Yantaishan Hospital, Yantai, Shandong 264000, P.R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Hu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005910:Glioma / Q000378:metabolism; D006801:Humans; D012503:Saponins / Q000494:pharmacology*; D051742:Transcription Factor CHOP / Q000378:metabolism
chemical_list: C000592854:3,15,18-trihydroxy-18,19-secolupane-12,19-dione 3-O-glucopyranosyl(1-2)glucopyranoside; D000972:Antineoplastic Agents, Phytogenic; D012503:Saponins; D051742:Transcription Factor CHOP