title: SAHA and/or MG132 reverse the aggressive phenotypes of glioma cells: An in vitro and vivo study.
abstract: To elucidate the anti-tumor effects and molecular mechanisms of SAHA (a histone deacetylase inhibitor) and MG132 (a proteasome inhibitor) on the aggressive phenotypes of glioma cells, we treated U87 and U251 cells with SAHA or/and MG132, and detected phenotypes' assays with phenotype-related molecules examined. It was found that SAHA or/and MG132 treatment suppressed proliferation in both concentration- and time-dependent manners, inhibited energy metabolism, migration, invasion and lamellipodia formation, and induced G2 arrest and apoptosis in the glioma cells. The treatment with SAHA increased the expression of acetyl-histones 3 and 4, which were recruited to the promoters of p21, p27, Cyclin D1, c-myc and Nanog to down-regulate their transcriptional levels. Expression of acetyl-histones 3 and 4 was higher in gliomas than normal brain tissues. Both drugs' exposure suppressed tumor growth in nude mice by inducing apoptosis and inhibiting proliferation, but increased serum aminotransferase and creatinine. These results indicated that SAHA and/or MG132 may suppress the aggressive phenotypes of glioma cells. They might be employed to treat the glioma if both hepatic and renal injuries are prevented.
authors.affiliation: Cancer Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China.
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Yang
authors.affiliation: Cancer Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China.
authors.forename: Zhi-Juan
authors.initials: ZJ
authors.lastname: Zhao
authors.affiliation: Cancer Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China.
authors.forename: Jia-Jie
authors.initials: JJ
authors.lastname: Liu
authors.affiliation: Department of Pathology, Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors.forename: Xiang-Hong
authors.initials: XH
authors.lastname: Yang
authors.affiliation: Cancer Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Cancer Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Cancer Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Shi
authors.affiliation: Department of Stomatology, The Second Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China.
authors.forename: Ke-Qiang
authors.initials: KQ
authors.lastname: Huang
authors.affiliation: Cancer Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China.|Life Science Institute of Jinzhou Medical University, Jinzhou 121001, China.
authors.forename: Hua-Chuan
authors.initials: HC
authors.lastname: Zheng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D018450:Disease Progression; D004734:Energy Metabolism / Q000187:drug effects; D015870:Gene Expression; D005910:Glioma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology*; D051379:Mice; D010641:Phenotype; D061988:Proteasome Inhibitors / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D007976:Leupeptins; D061988:Proteasome Inhibitors; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde
keywords: MG132; chemotherapy; glioma; histone acetylation; suberoylanilide hydroxamic acid