title: Wogonoside induces autophagy-related apoptosis in human glioblastoma cells.
abstract: Wogonoside, a bioactive flavonoid extracted from the root of Scutellaria baicalensis Georgi, has shown preclinical anticancer efficacy in various cancer models. However, the effects of wogonoside on glioblastoma cells remain unclear. In the present study, we found that wogonoside exhibited a cytotoxic effect on human glioblastoma cells. The suppression of cell viability was due to the induction of mitochondrial apoptosis. Furthermore, the presence of autophagic hallmarks, including an increase in punctate microtubule associated protein 1 light chain 3 (LC3) dots, changes in cellular morphology and increased levels of autophagy-related proteins were observed in the wogonoside-treated cells. Wogonoside treatment also enhanced autophagic flux as reflected by the increased acidic vesicular organelle (AVO) formation, p62 degradation and LC3 turnover. Notably, blockade of autophagy by a chemical inhibitor or RNA interference decreased the anticancer effect of wogonoside. In addition, the p38 mitogen-activated protein kinase (MAPK) signaling pathway, the phosphatidylinositide 3-kinase/protein kinase B/mammalian target of rapamycin/p70S6 kinase (PI3K/AKT/mTOR/p70S6K) signaling pathway and reactive oxygen species (ROS) participated in wogonoside-induced autophagy and apoptosis. These findings support the initiation of further studies of wogonoside as a candidate for the treatment of human malignant glioma.
authors: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu 210002, P.R. China.
authors: Li
authors: L
authors: Zhang
authors: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu 210002, P.R. China.
authors: Handong
authors: H
authors: Wang
authors: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu 210002, P.R. China.
authors: Zixiang
authors: Z
authors: Cong
authors: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu 210002, P.R. China.
authors: Jianguo
authors: J
authors: Xu
authors: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu 210002, P.R. China.
authors: Jianhong
authors: J
authors: Zhu
authors: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu 210002, P.R. China.
authors: Xiangjun
authors: X
authors: Ji
authors: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu 210002, P.R. China.
authors: Ke
authors: K
authors: Ding
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001343:Autophagy; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002525:Cerebellar Cortex / Q000166:cytology*; D044950:Flavanones / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D005960:Glucosides / Q000494:pharmacology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D044950:Flavanones; D005960:Glucosides; C473995:wogonoside