title: Hispidulin enhances the anti-tumor effects of temozolomide in glioblastoma by activating AMPK.
abstract: Glioblastoma is an aggressive malignancy, which is notorious for its poor prognosis. Although Temozolomide (TMZ) has been showed to be an effective chemotherapeutic agent for glioblastoma treatment, the response rate is far from satisfactory. As a natural compound with anti-cancer activity against a variety of cancers, Hispidulin is a good candidate drug for combination therapy. This study is designed to determine whether Hispidulin could potentiate the anti-tumor activity of TMZ in glioblastoma. Cell proliferation and apoptosis were determined by MTT assay and Hoechst staining, respectively. Expression of proteins relevant to apoptosis and proliferation was detected by Western blotting. Our in vitro assays showed that Hispidulin enhanced the anti-tumor activity of TMZ in glioblastoma by both inhibiting cell proliferation and inducing cell apoptosis. The anti-tumor activity of Hispidulin and the enhanced TMZ anti-tumor activity by Hispidulin induced the activation of AMPK signaling pathway. Our results showed that Hispidulin, by activating AMPK, exhibited anti-tumor activity and potentiated the anti-tumor activity of TMZ in glioblastoma. Although further preclinical and clinical studies are needed, this study provides insight for using Hispidulin as a chemosensitizing agent in clinic settings.
authors.affiliation: Department of Neurosurgery, Xijing Hospital of the Fourth Military Medical University, No. 127 West Changle Road, Xi'an, 710032, Shaanxi, People's Republic of China.
authors.forename: YanGang
authors.initials: Y
authors.lastname: Wang
authors.forename: WeiPing
authors.initials: W
authors.lastname: Liu
authors.forename: XiaoSheng
authors.initials: X
authors.lastname: He
authors.forename: Zhou
authors.initials: Z
authors.lastname: Fei
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D047309:Flavones / Q000494:pharmacology*; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D000077204:Temozolomide
chemical_list: D000970:Antineoplastic Agents; D047309:Flavones; D017382:Reactive Oxygen Species; D003606:Dacarbazine; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C055957:hispidulin; D000077204:Temozolomide