title: Inhibition of heme oxygenase-1 enhances anti-cancer effects of arsenic trioxide on glioma cells.
abstract: We have previously reported that arsenic trioxide (ATO) could inhibit glioma growth both in vitro and in vivo, and demonstrated its potent therapeutic effects on gliomas. In this study we showed that ATO induced cell damage and heme oxygenase-1 (HO-1) expression in glioma cells via ROS generation. HO-1 inducer clearly protected from ATO-induced cell death and ROS generation, and HO-1 inhibitor led to a significant increase in cell death and ROS generation induced by ATO. In addition, knockdown of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) strongly inhibited HO-1 expression induced by ATO, and significantly enhanced ATO-induced oxidative damage. Our results demonstrated, for the first time, that HO-1 inhibition or Nrf2 knockdown significantly potentiated ATO's effects on glioma cells. Considering that HO-1 is highly expressed in glioma tissues, administration of ATO in combination with either HO-1 inhibitor or Nrf2 knockdown may act as a new approach to the treatment of glioma.
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, The People's Republic of China.
authors.forename: Yaohua
authors.initials: Y
authors.lastname: Liu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liang
authors.forename: Tianhu
authors.initials: T
authors.lastname: Zheng
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.forename: Zhe
authors.initials: Z
authors.lastname: Sun
authors.forename: Changbin
authors.initials: C
authors.lastname: Shi
authors.forename: Shiguang
authors.initials: S
authors.lastname: Zhao
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D055785:Gene Knockdown Techniques; D005910:Glioma / Q000201:enzymology*; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors*; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D010087:Oxides / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D004791:Enzyme Inhibitors; D051267:NF-E2-Related Factor 2; D010087:Oxides; D017382:Reactive Oxygen Species; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D000077237:Arsenic Trioxide