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dc.contributor.authorKong, Yangen_US
dc.contributor.authorFeng, Zichaoen_US
dc.contributor.authorChen, Anjingen_US
dc.contributor.authorQi, Qichaoen_US
dc.contributor.authorHan, Mingzhien_US
dc.contributor.authorWang, Shuaien_US
dc.contributor.authorZhang, Yulinen_US
dc.contributor.authorZhang, Xinen_US
dc.contributor.authorYang, Ningen_US
dc.contributor.authorWang, Jiweien_US
dc.contributor.authorHuang, Binen_US
dc.contributor.authorZhang, Qingen_US
dc.contributor.authorXiang, Guoen_US
dc.contributor.authorLi, Wenjieen_US
dc.contributor.authorZhang, Dien_US
dc.contributor.authorWang, Jianen_US
dc.contributor.authorLi, Xingangen_US
dc.date.accessioned2020-05-11T05:52:48Z
dc.date.available2020-05-11T05:52:48Z
dc.date.issued2019-09-27
dc.PublishedKong Y, Feng Z, Chen A, Qi Q, Han M, et al. The Natural Flavonoid Galangin Elicits Apoptosis, Pyroptosis, and Autophagy in Glioblastoma. Frontiers in Oncology. 2019;9:942eng
dc.identifier.issn2234-943X
dc.identifier.urihttps://hdl.handle.net/1956/22162
dc.description.abstractGalangin (GG), a flavonoid, elicits a potent antitumor activity in diverse cancers. Here, we evaluated the efficacy of GG in the treatment of human glioblastoma multiforme (GBM) and investigated the molecular basis for its inhibitory effects in the disease. GG inhibited viability and proliferation of GBM cells (U251, U87MG, and A172) in a dose-dependent manner (IC50 = 221.8, 262.5, 273.9 μM, respectively; P < 0.001; EdU, ~40% decrease at 150 μM, P < 0.001), and the number of colonies formed was significantly reduced (at 50 μM, P < 0.001). However, normal human astrocytes were more resistant to its cytotoxic effects (IC50 >450 μM). Annexin-V/PI staining was increased indicating that GG induced apoptosis in GBM cells (26.67 and 30.42%, U87MG and U251, respectively) and associated proteins including BAX and cleaved PARP-1 were increased (~3×). Cells also underwent pyroptosis as determined under phase-contrast microscopy. Knockdown of gasdermin E (GSDME), a protein involved in pyroptosis, alleviated pyroptosis induced by GG through aggravating nuclear DNA damage in GBM cells. Meanwhile, fluorescent GFP-RFP-MAP1LC3B puncta associated with autophagy increased under GG treatment, and transmission electron microscopy confirmed the formation of autophagic vesicles. Inhibition of autophagy enhanced GG-induced apoptosis and pyroptosis in GBM cells. Finally, in an orthotopic xenograft model in nude mice derived from U87MG cells, treatment with GG in combination with an inhibitor of autophagy, chloroquine, suppressed tumor growth, and enhanced survival compared to GG monotherapy (P < 0.05). Our results demonstrated that GG simultaneously induces apoptosis, pytoptosis, and protective autophagy in GBM cells, indicating that combination treatment of GG with autophagy inhibitors may be an effective therapeutic strategy for GBM.en_US
dc.language.isoengeng
dc.publisherFrontiers Mediaeng
dc.rightsAttribution CC BYeng
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/eng
dc.subjectapoptosiseng
dc.subjectautophagyeng
dc.subjectgalangineng
dc.subjectpyroptosiseng
dc.subjectGlioblastomaeng
dc.titleThe Natural Flavonoid Galangin Elicits Apoptosis, Pyroptosis, and Autophagy in Glioblastomaen_US
dc.typePeer reviewed
dc.typeJournal article
dc.date.updated2019-12-10T14:15:49Z
dc.description.versionpublishedVersionen_US
dc.rights.holderCopyright 2019 The Author(s)
dc.identifier.doihttps://doi.org/10.3389/fonc.2019.00942
dc.identifier.cristin1753878
dc.source.journalFrontiers in Oncology


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