title: Wogonoside induces autophagy in MDA-MB-231 cells by regulating MAPK-mTOR pathway.
abstract: Previous studies have demonstrated that wogonoside, a bioactive flavonoid extracted from the root of Scutellaria baicalensis Gerogi, has anti-inflammatory and anti-angiogenic activities. In this study, we evaluated wogonoside-induced autophagy on human breast MDA-MB-231 cells. We report that wogonoside triggered the formation of microtubule-associated protein-light chain 3 (MAP-LC3) positive autophagosomes and the accumulation of acidic vesicular and autolysosomes in MDA-MB-231 cells. In addition, cells treated by wogonoside developed autophagosome-like characteristics, including single and double membrane vacuoles containing intact and degraded cellular debris. The results showed that wogonoside promotes the expression of LC3-II and Beclin-1. Furthermore, wogonoside inhibited cell growth of MDA-MB-231 cells in a concentration- and time-dependent manner, which was associated with wogonoside-induced autophagy. Wogonoside also suppressed the activation of mammalian target of rapamycin (mTOR) and p70-S6 kinase (p70S6K) by regulating the expression of the extracellular signal-regulated kinase (ERK1/2) and p38 involved mitogen-activated protein kinase (MAPK) signaling pathway. Taken together, these results suggest that wogonoside partially inhibits MDA-MB-231 cell growth by inducing autophagy through the MAPK-mTOR pathway and may be a promising anti-tumor agent.
authors.affiliation: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China. yj7782@126.com
authors.forename: Yajing
authors.initials: Y
authors.lastname: Sun
authors.forename: Meijuan
authors.initials: M
authors.lastname: Zou
authors.forename: Chen
authors.initials: C
authors.lastname: Hu
authors.forename: Yansu
authors.initials: Y
authors.lastname: Qin
authors.forename: Xiuming
authors.initials: X
authors.lastname: Song
authors.forename: Na
authors.initials: N
authors.lastname: Lu
authors.forename: Qinglong
authors.initials: Q
authors.lastname: Guo
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D044950:Flavanones / Q000494:pharmacology*; D005960:Glucosides / Q000494:pharmacology*; D006801:Humans; D008247:Lysosomes / Q000187:drug effects; D008565:Membrane Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014617:Vacuoles / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D044950:Flavanones; D005960:Glucosides; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C546842:MTOR protein, human; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C473995:wogonoside