Abstract:
:Ras signaling is often dysregulated and plays essential roles for the maintenance of glioblastoma. The proper function of Ras depends largely on the appropriate post-translational modification termed prenylation. Targeting protein prenylation therefore represents an alternative therapeutic strategy in glioblastoma. In this study, we demonstrate that prenylation inhibition by atorvastatin is active against glioblastoma. Atorvastatin alone dose-dependently inhibits growth and survival of multiple glioblastoma cell lines. Its combination with temozolomide significantly enhances temozolomide's efficacy in in vitro cultured cell system as well as in vivo xenograft glioblastoma tumor model. We further show that this is achieved by the inhibition of Ras prenylation, leading to decreased activation of Ras and its downstream signaling pathways, including Erk, rS6 and eIF4E. Our findings suggest that inhibition of Ras activity by atorvastatin effectively targets the MEK and other signaling pathways. Our study provides a fundamental evidence to repurpose atorvastatin for a potential treatment of glioblastoma.
journal_name
Biochem Biophys Res Communjournal_title
Biochemical and biophysical research communicationsauthors
Peng P,Wei W,Long C,Li Jdoi
10.1016/j.bbrc.2017.05.147subject
Has Abstractpub_date
2017-07-29 00:00:00pages
293-298issue
3eissn
0006-291Xissn
1090-2104pii
S0006-291X(17)31047-1journal_volume
489pub_type
杂志文章abstract::Cigarette smoke (CS)-induced emphysema is attributable to matrix metalloproteinase-12 (MMP-12) in mice, however, a relationship between CS and MMP-12 is absent in human emphysema. Here, we show that cigarette smoke condensate (CSC) induces MMP-12 gene expression in airway-like epithelia through a hydrogen peroxide (H(...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2005.02.144
更新日期:2005-04-29 00:00:00
abstract::Previous reports have shown that 12-0-tetradecanoylphorbol-13-acetate can activate phospholipase D in human peripheral blood mononuclear cells as measured by an enzyme-catalyzed transphosphatidylation reaction (phosphatidylethanol formation). In the present study, the mononuclear cells were fractionated by two procedu...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/0006-291x(89)92379-6
更新日期:1989-07-31 00:00:00
abstract::Signaling via the type 1 insulin-like growth factor receptor (IGF1R) confers resistance to EGF receptor (EGFR) inhibitors. It is plausible that reciprocal EGFR compensation could mediate resistance to IGF1R inhibition, prompting us to investigate effects of IGF1R depletion on EGFR signaling in breast cancer cells expr...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2007.02.041
更新日期:2007-04-13 00:00:00
abstract::OPA1 is a cause gene for autosomal dominant optic atrophy and possesses eight alternative splicing variants. Here, we identified two isoforms of OPA1 proteins in HeLa cells and examined their submitochondrial localization and complex formations. RT-PCR shows that HeLa cells mainly express isoforms 7 and 1 of OPA1. Sin...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/s0006-291x(02)02874-7
更新日期:2003-01-10 00:00:00
abstract::Poly(ADP-ribose) polymerase (ADPRP) is a nuclear enzyme that transfers ADP-ribose from NAD+ to diverse nuclear proteins. Previously, the function of ADPRP was considered to relate exclusively to its catalytic activity. However, recent experiments have shown that ADPRP is actually an abundant DNA-binding protein, and t...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/0006-291x(89)92336-x
更新日期:1989-09-15 00:00:00
abstract::An 18-kDa lectin, with an N-terminal sequence displaying slight similarity to some lectins and fungal immunomodulatory proteins, was isolated from the mushroom Ganoderma capense (Lloyd) Teng. It exhibited more potent mitogenic activity than that of concanavalin A toward mouse splenocytes, and antiproliferative activit...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2003.12.196
更新日期:2004-02-20 00:00:00
abstract::The number of accessible SH-groups was determined in membrane vesicles prepared from Escherichia coli growing in fermentation conditions at slightly alkaline pH on glucose with or without added formate. Addition of ATP or formate to the vesicles caused a approximately 1.4-fold increase in the number of accessible SH-g...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/s0006-291x(03)01460-8
更新日期:2003-08-29 00:00:00
abstract::The conversion of the endogenous cellular prion protein to an abnormally folded isoform is a hallmark of transmissible spongiform encephalopathies. It occurs when a misfolded prion protein contacts the cellular PrP. Among the molecular partners suggested to be involved in the misfolding process, the glycosaminoglycans...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2011.09.126
更新日期:2011-10-28 00:00:00
abstract::We have previously indicated that Xenopus Suppressor of Hairless 2, XSu(H)2, is involved in the morphogenesis of gastrula embryos in a different manner from the XESR-1-mediated Notch signaling pathway. To address the downstream factors of XSu(H)2, we investigated the effect of XSu(H)2 on XenopusPOU-V genes, Xoct25 and...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2006.12.087
更新日期:2007-02-16 00:00:00
abstract::A murine genomic clone of about 16 kilobases encompassing putatively entire bone morphogenetic protein (BMP)-4 gene has been isolated. Comparison with the cDNA clones revealed the existence of at least five exons on the 3' side of the clone. There are two alternative transcriptional start sites, one is for the first e...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.1993.1523
更新日期:1993-05-14 00:00:00
abstract::Actin binding protein from human blood platelets is shown to exist in the resting platelet as a phosphorylated protein and contains two residues of phosphate per 260,000 kd. Removal of one-half of these residues with E. coli alkaline phosphatase results in the loss of its ability to crosslink F-actin into a low speed ...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/0006-291x(84)91332-9
更新日期:1984-01-30 00:00:00
abstract::In a simple salts medium, monolayers of IEC-6 intestinal cells achieved concentrations of unmetabolized formycin B (an analog of inosine) about 6-fold higher than in the medium. Rates of formycin B influx were a saturable function of Na+ concentrations in the medium. Although IEC-6 cells possess sites with high affini...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/0006-291x(86)90738-2
更新日期:1986-11-14 00:00:00
abstract::The smallest protein of hepatitis B virus, HBX, has been implicated in the development of liver diseases by interfering with normal cellular processes. Its role in cell proliferation has been unclear as both pro-apoptotic and anti-apoptotic activities have been reported. We showed molecular evidence that HBX induced a...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2005.10.117
更新日期:2005-12-23 00:00:00
abstract::Transforming growth factor-beta (TGF-beta) is crucially virulent in the progression of fibrotic disorders. TAK1 (TGF-beta activated kinase 1) is one of the mitogen-activated kinase kinase kinase (MAPKKK) that is involved in TGF-beta signal transduction. To elucidate the importance of TAK1 in TGF-beta-induced fibrotic ...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/s0006-291x(03)01207-5
更新日期:2003-07-25 00:00:00
abstract::Although mutations and deletions in the p53 tumor suppressor gene lead to resistance to low linear energy transfer (LET) radiation, high-LET radiation efficiently induces cell lethality and apoptosis regardless of the p53 gene status in cancer cells. Recently, it has been suggested that the induction of p53-independen...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2012.06.004
更新日期:2012-07-13 00:00:00
abstract::A method has been developed for the specific amplification and cloning of human hprt cDNA which can be used for mutant sequence analysis. Messenger RNA is isolated from TK6 lymphoblasts and is used to produce a first strand cDNA with reverse transcriptase primed with oligo dT. Second strand synthesis and subsequent am...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/0006-291x(88)90619-5
更新日期:1988-02-29 00:00:00
abstract::Focal adhesion kinase, FAK, is a unique protein tyrosine kinase found in cellular focal adhesions. It is widely expressed and highly phosphorylated during embryogenesis. To examine the function of FAK in cell differentiation, we made FAK-deficient embryonic stem (ES) cells by homologous recombination. However, FAK-def...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.1995.1503
更新日期:1995-04-06 00:00:00
abstract::Oleanolic acid (OA), a pentacyclic triterpene acid, is reported to have antitumor activities; however, the mechanism underlying its antitumorigenic effects is poorly understood. To further determine the mechanism of OA, we investigated the effects of OA on the release of nitric oxide (NO) and tumor necrosis factor-alp...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.2001.5727
更新日期:2001-10-19 00:00:00
abstract::Tyrosine hydroxylase (TH) is the rate-limiting enzyme in catecholamine biosynthesis, and its N-terminus plays a critical role in the intracellular stability of the enzyme. In the present study, we investigated the mechanism by which the N-terminal region of TH affects this stability. TH molecules phosphorylated at the...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2011.03.020
更新日期:2011-04-08 00:00:00
abstract::Cancer cells enhance autophagic activity as a survival measure against metabolic and therapeutic stresses. The inhibition of autophagy may represent a valuable sensitizing target for cancer treatment. Recently, we examined the ability of various cytochalasins to inhibit autophagy and demonstrated the potent inhibitory...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2018.03.029
更新日期:2018-04-06 00:00:00
abstract::Precise control of neuronal migration is essential for the development of the neocortex. However, the molecular mechanisms underlying neuronal migration remain largely unknown. Here we identified helix-loop-helix transcription factor Ebf3 as a Prdm8 target gene, and found that Ebf3 is a key regulator of neuronal migra...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2017.11.021
更新日期:2018-01-01 00:00:00
abstract::PKM2 is an isoenzyme of the glycolytic enzyme pyruvate kinase that promotes aerobic glycolysis. Here, we describe an important role for PKM2 in regulating the survival of gastric cancer (GC) cells. We showed that PKM2 was overexpressed in gastric tumor tissues compared to normal tissues and its expression level was as...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2012.05.063
更新日期:2012-06-22 00:00:00
abstract::Intracerebral hemorrhage (ICH) is reported as a common and often fatal type of stroke accompanied with high morbidity and mortality, and it frequently results in long-lasting neurological dysfunctions. However, the pathogenesis that contributes to ICH has not been fully understood. Rnf112, also known as Znf179, is a m...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2018.10.141
更新日期:2018-12-09 00:00:00
abstract::2-((2-Pyridylmethyl)sulfinyl)benzimidazoles, selective inhibitors of the H+/K+-ATPase in the parietal cells of the stomach, have been investigated concerning their chemical behaviour in acidic medium. Protonation of the sulfoxide and subsequent elimination of water forms a sulfenium ion or a chemical equivalent thereo...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/0006-291x(85)91703-6
更新日期:1985-04-16 00:00:00
abstract::PhyA gene products of Aspergillus ficuum (AF) and Peniophora lycii (PL) as expressed in industrial strains of Aspergillus niger and Aspergillus oryzae, respectively, were purified to homogeneity and then characterized for both physical and biochemical properties. The PL phytase is 26 amino acid residues shorter than t...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/s0006-291x(03)00374-7
更新日期:2003-04-04 00:00:00
abstract::TESK1 (testis-specific protein kinase 1) is a serine/threonine kinase, with a unique structure composed of an N-terminal protein kinase domain and a C-terminal proline-rich domain. Northern blot analysis revealed that TESK1 mRNA is predominantly expressed in testicular germ cells. We present here evidence that express...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.1998.9099
更新日期:1998-08-10 00:00:00
abstract::Inhibitor of apoptosis proteins (IAPs) such as XIAP, cIAP1, and cIAP2 are upregulated in many cancer cells. Several compounds targeting IAPs and inducing cell death in cancer cells have been developed. Some of these are synthesized mimicking the N-terminal tetrapeptide sequence of Smac/DIABLO, the natural endogenous I...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2008.10.139
更新日期:2009-01-09 00:00:00
abstract::It is still unclear whether an active state of transcription once established in chromatin persists in neurons. Here, we focused on BDNF exon I-IX mRNA expression because of its marked induction upon the treatment of rat cortical neurons with trichostatin A, suggesting strong repression of the expression through histo...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1016/j.bbrc.2009.10.021
更新日期:2009-12-18 00:00:00
abstract::Because of their structural similarity and ubiquitous distribution as actin binding proteins, plant profilins represent important cross-reactive allergens for almost 20% of patients suffering from Type I allergy to pollen and other plant products. The cDNAs coding for three birch profilin variants (Tyr44, Glu47, and A...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.1996.1309
更新日期:1996-09-04 00:00:00
abstract::The human pregnancy-specific glycoprotein (PSG) family consists of eleven closely related molecules mainly synthesized by placental syncytiotrophoblasts and whose function(s) are unknown. They belong to the carcinoembryonic antigen (CEA) family. As a step toward understanding PSG function, we have analysed 84 PSG cDNA...
journal_title:Biochemical and biophysical research communications
pub_type: 杂志文章
doi:10.1006/bbrc.1995.1862
更新日期:1995-06-15 00:00:00