当前位置： SCI文献检索 > ONCOGENE期刊下所有文献 > Silibinin inhibits hypoxia-inducible factor-1alpha and mTOR/p70S6K/4E-BP1 signalling pathway in human cervical and hepatoma cancer cells: implications for anticancer therapy.

Silibinin inhibits hypoxia-inducible factor-1alpha and mTOR/p70S6K/4E-BP1 signalling pathway in human cervical and hepatoma cancer cells: implications for anticancer therapy.

Abstract：

:The hypoxia-inducible factor 1 (HIF-1) plays a critical role for tumour adaptation to microenvironmental hypoxia, and represents an appealing chemotherapeutic target. Silibinin is a nontoxic flavonoid reported to exhibit anticancer properties. However, the mechanisms by which silibinin inhibits tumour growth are not fully understood. In this study, silibinin was found to inhibit hypoxia-induced HIF-1alpha accumulation and HIF-1 transcriptional activity in human cervical (HeLa) and hepatoma (Hep3B) cells. Neither HIF-1alpha protein degradation rate nor HIF-1alpha steady-state mRNA level was affected by silibinin. Rather, we found that suppression of HIF-1alpha accumulation by silibinin correlated with strong dephosphorylation of mammalian target of rapamycin (mTOR) and its effectors ribosomal protein S6 kinase (p70S6K) and eukaryotic initiation factor 4E-binding protein-1 (4E-BP1), a pathway known to regulate HIF-1alpha expression at the translational level. Silibinin also activated Akt, a mechanistic feature exhibited by established mTOR inhibitors in many tumour cells. Moreover, silibinin reduced hypoxia-induced vascular endothelial growth factor (VEGF) release by HeLa and Hep3B cells, and this effect was potentiated by the PI3K/Akt inhibitor LY294002. Finally, silibinin was found to be a potent inhibitor of cell proliferation. These results show that silibinin is an effective inhibitor of HIF-1 and provide new perspectives into the mechanism of its anticancer activity.

journal_name

Oncogene

journal_title

Oncogene

authors

García-Maceira P,Mateo J

doi

10.1038/onc.2008.398

subject

Has Abstract

pub_date

2009-01-22 00:00:00

pages

313-24

issue

3

eissn

0950-9232

issn

1476-5594

pii

onc2008398

journal_volume

28

pub_type

杂志文章

相关文献

ONCOGENE文献大全
  • The FoxO code.

    abstract：:The FoxO family of Forkhead transcription factors plays an important role in longevity and tumor suppression by upregulating target genes involved in stress resistance, metabolism, cell cycle arrest and apoptosis. FoxO transcription factors translate a variety of environmental stimuli, including insulin, growth factor...

    journal_title：Oncogene

    pub_type： 杂志文章,评审

    doi：10.1038/onc.2008.21

    authors： Calnan DR,Brunet A

    更新日期：2008-04-07 00:00:00

  • Suppression of v-Src transformation in primary rat embryo fibroblasts.

    abstract：:To understand the mechanism for resistance of primary cultures of rat embryo fibroblasts (REFs) to oncogene-induced transformation, we studied the transforming ability of a recombinant retrovirus, ZSV, containing v-src and neo genes in REFs and in the rat cell line F2408. The susceptibility of REFs to p60v-src transfo...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：

    authors： Inoue H,Tavoloni N,Hanafusa H

    更新日期：1995-07-20 00:00:00

  • Interleukin 1 induces an autocrine loop hepatocyte growth factor/c-Met in murine Kaposi-like spindle cells.

    abstract：:Several cytokines, growth factors and the HIV transactivator Tat were shown to be involved in the pathogenesis of Kaposi's sarcoma. BKV/tat transgenic mice develop Kaposi's sarcoma-like lesions, and spindle-shaped cells (TTB) have been derived from these lesions. Here we show that TTB cells co-express hepatocyte growt...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：

    authors： Maier J,Mariotti M,Comoglio PM,Soria MR

    更新日期：1996-09-05 00:00:00

  • Loss of claudin-3 expression induces IL6/gp130/Stat3 signaling to promote colon cancer malignancy by hyperactivating Wnt/β-catenin signaling.

    abstract：:The hyperactivated Wnt/β-catenin signaling acts as a switch to induce epithelial to mesenchymal transition and promote colorectal cancer. However, due to its essential role in gut homeostasis, therapeutic targeting of this pathway has proven challenging. Additionally, IL-6/Stat-3 signaling, activated by microbial tran...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/onc.2017.259

    authors： Ahmad R,Kumar B,Chen Z,Chen X,Müller D,Lele SM,Washington MK,Batra SK,Dhawan P,Singh AB

    更新日期：2017-11-23 00:00:00

  • Molecular requirements for transcriptional initiation of the murine c-myc gene.

    abstract：:We have identified sequences in the 5' flanking region of the murine c-myc gene's P1 and P2 transcription initiation sites which form specific complexes with nuclear factors of murine and human origin and are also required for normal P1 and P2 usage. Four nuclear factor binding sites were identified within 400 bp 5' o...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：

    authors： Asselin C,Nepveu A,Marcu KB

    更新日期：1989-05-01 00:00:00

  • Apc deficiency predisposes to renal carcinoma in the mouse.

    abstract：:Deregulation of Wnt signalling has recently been implicated in human renal cancer. Here, we directly test this association by using a Cre-LoxP strategy to inactivate the Adenomatous Polyposis Coli (Apc) gene in the murine renal epithelium. Mice homozygous for a conditional Apc allele were intercrossed with mice transg...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1208956

    authors： Sansom OJ,Griffiths DF,Reed KR,Winton DJ,Clarke AR

    更新日期：2005-12-08 00:00:00

  • Overexpression of CD44 in pl85(neu)-transfected NIH3T3 cells promotes an up-regulation of hyaluronic acid-mediated membrane-cytoskeleton interaction and cell adhesion.

    abstract：:CD44 is a transmembrane glycoprotein known to bind hyaluronic acid (HA) in its extracellular domain and to contain at least one ankyrin-binding site in its cytoplasmic domain. In this study we have examined CD44 expression in a mouse fibroblast cell line transfected with the pl85(neu) oncogene cDNA. The results of RT-...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：

    authors： Zhu D,Bourguignon L

    更新日期：1996-06-06 00:00:00

  • Alternate mechanisms of ras activation are complementary and favor and formation of ras-GTP.

    abstract：:The mechanisms of ras activation by mutations in residue 61 and in the NKXD guanine nucleotide-binding consensus sequence (ras residues 116-119) have been evaluated. Weakly transforming mutations that either reduce intrinsic and GTPase-activating protein (GAP)-stimulated GTPase activities (61P) or enhance guanine nucl...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：

    authors： Patel G,MacDonald MJ,Khosravi-Far R,Hisaka MM,Der CJ

    更新日期：1992-02-01 00:00:00

  • HER2/Neu: mechanisms of dimerization/oligomerization.

    abstract：:DOI: 10.1038/sj/onc/1205119 ...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1205119

    authors： Brennan PJ,Kumagai T,Berezov A,Murali R,Greene MI

    更新日期：2002-01-10 00:00:00

  • Localization of chromosome 8p regions involved in early tumorigenesis of oral and laryngeal squamous carcinoma.

    abstract：:We analysed 30 primary invasive oral and laryngeal squamous carcinomas (SC), with concurrent dysplastic lesions, for genetic alterations at 15 microsatellite loci on the short arm of chromosome 8. Overall, loss of heterozygosity (LOH) was observed, in at least one informative locus, in 27% of the dysplastic lesions an...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1201808

    authors： El-Naggar AK,Coombes MM,Batsakis JG,Hong WK,Goepfert H,Kagan J

    更新日期：1998-06-11 00:00:00

  • Bcl-2 inhibits hydrogen peroxide-induced ER Ca2+ pool depletion.

    abstract：:The mechanism by which Bcl-2 inhibits apoptosis is unknown. The Bcl-2 protein is localized to intracellular membranes, including the endoplasmic reticulum (ER). The ER is the major intracellular reservoir of Ca2+ in non-muscle cells, sequestering Ca2+ for use in intracellular signaling, and is a prime target of oxidat...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：

    authors： Distelhorst CW,Lam M,McCormick TS

    更新日期：1996-05-16 00:00:00

  • Activation of Stat5 by platelet-derived growth factor (PDGF) is dependent on phosphorylation sites in PDGF beta-receptor juxtamembrane and kinase insert domains.

    abstract：:Signal transducers and activators of transcription (Stats) are known to transduce signals from the cell surface to the nucleus in cytokine receptor signaling. We examined the capacity of platelet-derived growth factor (PDGF) receptor to interact with and activate Stat molecules. Activation of the PDGF beta-receptor le...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1201555

    authors： Valgeirsdóttir S,Paukku K,Silvennoinen O,Heldin CH,Claesson-Welsh L

    更新日期：1998-01-29 00:00:00

  • The transcriptional corepressor MTG16a contains a novel nucleolar targeting sequence deranged in t (16; 21)-positive myeloid malignancies.

    abstract：:The MTG (Myeloid Translocation Gene) proteins are a family of novel transcriptional corepressors. We report that MTG16a, a protein isoform encoded by the MTG16 gene deranged by the t (16; 21) in myeloid malignancies, is targeted to the nucleolus. The amino acid sequence necessary for nucleolar localization was mapped ...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1205882

    authors： Hoogeveen AT,Rossetti S,Stoyanova V,Schonkeren J,Fenaroli A,Schiaffonati L,van Unen L,Sacchi N

    更新日期：2002-09-26 00:00:00

  • Developmental expression of pim kinases suggests functions also outside of the hematopoietic system.

    abstract：:We have cloned a novel quail cDNA with strong homology to the pim family of proto-oncogenes. The deduced amino acid (aa) sequence of the cDNA, named qpim, is more closely related to Xenopus Pim and to the recently identified rat Pim-3 than to human or rodent Pim-1 or Pim-2. The protein encoded by the qpim cDNA can aut...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1203355

    authors： Eichmann A,Yuan L,Bréant C,Alitalo K,Koskinen PJ

    更新日期：2000-02-24 00:00:00

  • Selective maternal-allele loss in human lung cancers of the maternally expressed p57KIP2 gene at 11p15.5.

    abstract：:Genomic imprinting at 11p15 is suggested to play a role in certain pediatric tumors such as Wilms' tumor, based on the findings of selective maternal loss of this chromosomal region. Although the allele loss at 11p15 is also frequent in a number of cancers of adults including lung, breast, and bladder cancers, possibl...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：

    authors： Kondo M,Matsuoka S,Uchida K,Osada H,Nagatake M,Takagi K,Harper JW,Takahashi T,Elledge SJ,Takahashi T

    更新日期：1996-03-21 00:00:00

  • Knockdown of Sox4 expression by RNAi induces apoptosis in ACC3 cells.

    abstract：:Microarray RNA gene expression profiling analysis has shown that Sox4 (Sry-related high mobility group (HMG) box 4) is one of the most upregulated genes in adenoid cystic carcinoma (ACC), relative to non-neoplastic tissue of origin. Here, we show that Sox4 protein is similarly upregulated in ACC by immunohistochemistr...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1209566

    authors： Pramoonjago P,Baras AS,Moskaluk CA

    更新日期：2006-09-14 00:00:00

  • The autophagic paradox in cancer therapy.

    abstract：:Autophagy, hallmarked by the formation of double-membrane bound organelles known as autophagosomes, is a lysosome-dependent pathway for protein degradation. The role of autophagy in carcinogenesis is context dependent. As a tumor-suppressing mechanism in early-stage carcinogenesis, autophagy inhibits inflammation and ...

    journal_title：Oncogene

    pub_type： 杂志文章,评审

    doi：10.1038/onc.2011.295

    authors： Wu WK,Coffelt SB,Cho CH,Wang XJ,Lee CW,Chan FK,Yu J,Sung JJ

    更新日期：2012-02-23 00:00:00

  • Soluble CD44 inhibits melanoma tumor growth by blocking cell surface CD44 binding to hyaluronic acid.

    abstract：:Proteolytic cleavage of the extracellular domain of CD44 from the surface of cells has been observed recently in different cell types. In cell culture supernatants of human melanoma cell lines a 70 kDa soluble CD44 protein (solCD44) was detected at concentrations of 250-300 ng/ml. Protease inhibitor studies revealed t...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1204435

    authors： Ahrens T,Sleeman JP,Schempp CM,Howells N,Hofmann M,Ponta H,Herrlich P,Simon JC

    更新日期：2001-06-07 00:00:00

  • Adenovirus E1a as a tumor-suppressor gene.

    abstract：:The E1a gene of group C adenoviruses is one of the most studied transforming genes of DNA tumor viruses. These transforming genes have been conventionally considered as dominant oncogenes since they transform cells in vitro and many of the resulting transformed cell lines induce tumors in experimental animals. It now ...

    journal_title：Oncogene

    pub_type： 杂志文章,评审

    doi：

    authors： Chinnadurai G

    更新日期：1992-07-01 00:00:00

  • Analysis of TEL proteins in human leukemias.

    abstract：:Chromosomal translocations involving the human 12p13 band frequently affect the TEL gene, usually resulting in gene fusion between TEL and genes encoding proteins of various types. The most frequent 12p13 translocation is the t(12;21)(p13;q22), which recombines TEL with the AML1 gene on chromosome 21 and is frequently...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1201817

    authors： Poirel H,Lacronique V,Mauchauffé M,Le Coniat M,Raffoux E,Daniel MT,Erickson P,Drabkin H,MacLeod RA,Drexler HG,Ghysdael J,Berger R,Bernard OA

    更新日期：1998-06-04 00:00:00

  • Copine-III interacts with ErbB2 and promotes tumor cell migration.

    abstract：:ErbB2 amplification and overexpression in breast cancer correlates with aggressive disease and poor prognosis. To find novel ErbB2-interacting proteins, we used stable isotope labeling of amino acids in cell culture followed by peptide affinity pull-downs and identified specific binders using relative quantification b...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/onc.2009.456

    authors： Heinrich C,Keller C,Boulay A,Vecchi M,Bianchi M,Sack R,Lienhard S,Duss S,Hofsteenge J,Hynes NE

    更新日期：2010-03-18 00:00:00

  • The human papillomavirus E6 protein and its contribution to malignant progression.

    abstract：:The human papillomavirus (HPV) E6 protein is one of three oncoproteins encoded by the virus. It has long been recognized as a potent oncogene and is intimately associated with the events that result in the malignant conversion of virally infected cells. In order to understand the mechanisms by which E6 contributes to ...

    journal_title：Oncogene

    pub_type： 杂志文章,评审

    doi：10.1038/sj.onc.1204869

    authors： Mantovani F,Banks L

    更新日期：2001-11-26 00:00:00

  • The cellular transcription factor Brn-3a and the smoking-related substance nicotine interact to regulate the activity of the HPV URR in the cervix.

    abstract：:The cellular transcription factor Brn-3a differentially regulates different human papilloma virus (HPV)-16 variants that are associated with different risks of progression to cervical carcinoma in infected humans. The upstream regulatory regions (URRs) of high- and intermediate-risk HPV-16 variants are activated by th...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/onc.2010.33

    authors： Ndisang D,Khan A,Lorenzato F,Sindos M,Singer A,Latchman DS

    更新日期：2010-05-06 00:00:00

  • Functional homology between N-myc and c-myc in murine plasmacytomagenesis: plasmacytoma development in N-myc transgenic mice.

    abstract：:Mouse plasmacytomas induced by pristane oil alone, or in combination with Abelson murine leukemia virus (A-MuLV), regularly carry one of three alternative chromosomal translocations that juxtapose c-myc to immunoglobulin heavy- or light-chain loci. E mu-c-myc transgenic mice develop translocation-free plasmacytomas af...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：

    authors： Wang Y,Sugiyama H,Axelson H,Panda CK,Babonits M,Ma A,Steinberg JM,Alt FW,Klein G,Wiener F

    更新日期：1992-06-01 00:00:00

  • Localization of a growth suppressor activity in MCF7 breast cancer cells to chromosome 17q24-q25.

    abstract：:Chromosome 17 is one of the most frequently altered chromosomes in malignant breast cancer. At least four genes implicated in breast cancer reside on chromosome 17 (p53, 17p13; Her-2/neu/ERBB2, 17q12; BRCA1, 17q21; and nm23, 17q22). In addition, allelic imbalance has been described for at least five regions of chromos...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1201073

    authors： Plummer SJ,Adams L,Simmons JA,Casey G

    更新日期：1997-05-15 00:00:00

  • Expression of tetraspanins in human lung cancer cells: frequent downregulation of CD9 and its contribution to cell motility in small cell lung cancer.

    abstract：:Small cell lung cancer (SCLC) invades locally and metastasizes distantly extremely early when compared with nonsmall cell lung cancer (NSCLC). The underlying molecular mechanisms, however, have not been elucidated. Accumulating evidence suggests that downregulation of several members of tetraspanins is associated with...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1206106

    authors： Funakoshi T,Tachibana I,Hoshida Y,Kimura H,Takeda Y,Kijima T,Nishino K,Goto H,Yoneda T,Kumagai T,Osaki T,Hayashi S,Aozasa K,Kawase I

    更新日期：2003-02-06 00:00:00

  • C-myb proto-oncogene: evidence for intermolecular recombination of coding sequences.

    abstract：:We have characterized a novel chicken c-myb exon whose sequences are specifically expressed in thymic cells. In situ hybridization experiments indicate that this thymus-specific coding exon is localized on a small chromosome, distinct from the large acrocentric chromosome 3 on which we recently mapped the bulk of 15 e...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：

    authors： Vellard M,Soret J,Viegas-Pequignot E,Galibert F,Nguyen VC,Dutrillaux B,Perbal B

    更新日期：1991-04-01 00:00:00

  • Alterations in growth properties of human papilloma virus type 16 immortalised human cervical keratinocyte cell line correlate with amplification and overexpression of c-myc oncogene.

    abstract：:Clinical and epidemiological data support a role for human papilloma virus (HPV) type 16 in the pathogenesis of cervical carcinoma. The W12 cell line contains HPV16 sequences, predominantly as a high copy number episome, and is immortalised in vitro, but non-tumourigenic. A morphologically distinct sub-line of the par...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：

    authors： Crook T,Greenfield I,Howard J,Stanley M

    更新日期：1990-04-01 00:00:00

  • The VHL tumor suppressor inhibits expression of the IGF1R and its loss induces IGF1R upregulation in human clear cell renal carcinoma.

    abstract：:Clear cell renal cell cancer (CC-RCC) is a highly chemoresistant tumor characterized by frequent inactivation of the von Hippel-Lindau (VHL) gene. The prognosis is reportedly worse in patients whose tumors express immunoreactive type I insulin-like growth factor receptor (IGF1R), a key mediator of tumor cell survival....

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1210474

    authors： Yuen JS,Cockman ME,Sullivan M,Protheroe A,Turner GD,Roberts IS,Pugh CW,Werner H,Macaulay VM

    更新日期：2007-10-04 00:00:00

  • Regulation of the cell cycle by p53 after DNA damage in an amphibian cell line.

    abstract：:In mammalian cells, the p53 protein is a key regulator of the cell cycle following DNA damage. In the present study, we investigated the function of p53 in the A6 amphibian cell line. Using various specific Xenopus p53 monoclonal antibodies, we showed that Xenopus p53 accumulates after DNA damage, including gamma and ...

    journal_title：Oncogene

    pub_type： 杂志文章

    doi：10.1038/sj.onc.1204492

    authors： Bensaad K,Rouillard D,Soussi T

    更新日期：2001-06-28 00:00:00