Induction of apoptosis by the proteasome inhibitor MG132 in human HCC cells: Possible correlation with specific caspase-dependent cleavage of beta-catenin and inhibition of beta-catenin-mediated transactivation.

Abstract:

:Proteasome inhibitors, like MG132, can exert cell growth inhibitory and apoptotic effects in different tumor types. The apoptotic mechanism of these compounds involves the activation of the effector caspases. beta-catenin, also an oncogene, represents one of the substrates of these proteases, but the consequences of its cleavage are poorly understood. We investigated its function during apoptosis induced by MG132 in three hepatocellular carcinoma (HCC) cell lines, endowed (HepG2 and HuH-6) or not (HA22T/VGH) with activating mutations of beta-catenin. Induction of apoptosis was associated with cell growth inhibition, accumulation of the cells at the G(2)/M phases of the cell cycle, as well as with fragmentation of beta-catenin (but not of alpha- or gamma-catenin) in all the cell lines. The cleavage of beta-catenin was inhibited by the caspase inhibitors Z-VAD-fmk and Z-DEVD-fmk. Fragmented beta-catenin was found in the nuclei of the treated cells. Analyses through the reporter plasmid pTOPflash showed that MG132 significantly reduces Tcf transcriptional activity in the cells. This was associated with a decrease in the mRNA expression of survivin and c-myc, which are target genes of the APC/beta-catenin/Tcf signaling. Nevertheless, Z-VAD-fmk or Z-DEVD-fmk did not reverse the MG132 effects on Tcf transcriptional activity, suggesting that the compound may affect this activity also by other mechanisms. Overall, the present study supports the therapeutic potential of the proteasome inhibitors in HCC.

journal_name

Int J Mol Med

authors

Cervello M,Giannitrapani L,La Rosa M,Notarbartolo M,Labbozzetta M,Poma P,Montalto G,D'Alessandro N

subject

Has Abstract

pub_date

2004-05-01 00:00:00

pages

741-8

issue

5

eissn

1107-3756

issn

1791-244X

journal_volume

13

pub_type

杂志文章
  • Comparative integromics on FAT1, FAT2, FAT3 and FAT4.

    abstract::WNT5A, WNT5B, WNT11, FZD3, FZD6, VANGL1, VANGL2, DVL1, DVL2, DVL3, PRICKLE1, PRICKLE2, ANKRD6, NKD1, NKD2, DAAM1, DAAM2, CELSR1, CELSR2, CELSR3, ROR1 and ROR2 are planar cell polarity (PCP) signaling molecules implicated in the regulation of cellular polarity, convergent extension, and invasion. FAT1, FAT2, FAT3 and F...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:

    authors: Katoh Y,Katoh M

    更新日期:2006-09-01 00:00:00

  • Frequent microsatellite alterations in a predominantly younger age of onset breast cancer population.

    abstract::Microsatellite instability (MSI) and loss of heterozygosity (LOH) was investigated in paired tumour and normal tissue DNA from 108 predominantly premenopausal breast cancer patients (under age 45 years at presentation) for 25 simple repeat loci interspersed across 11 chromosomes. MSI was observed at a single locus in ...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.11.1.117

    authors: Luqmani YA,Mathew M,Lobo S

    更新日期:2003-01-01 00:00:00

  • Oxidant stress regulation of IL-8 and ICAM-1 gene expression: differential activation and binding of the transcription factors AP-1 and NF-kappaB (Review).

    abstract::Reactive oxygen species (ROS), generated either extracellularly or intracellularly through ligand-receptor interactions, can function as signal transduction molecules to activate the chemotactic cytokine interleukin-8 (IL-8) and the cell surface adhesion protein, intercellular adhesion molecule-1 (ICAM-1; CD54). Toget...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章,评审

    doi:10.3892/ijmm.4.3.223

    authors: Roebuck KA

    更新日期:1999-09-01 00:00:00

  • Hirschsprung, RET-SOX and beyond: the challenge of examining non-mendelian traits (Review).

    abstract::Hirschsprung disease (HSCR), or congenital intestinal aganglionosis, is a common hereditary disorder causing intestinal obstruction, thereby showing considerable phenotypic variation in conjunction with complex inheritance. Moreover, phenotypic assessment of the disease has been complicated since a subset of the obser...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章,评审

    doi:

    authors: Pusch CM,Sasiadek MM,Blin N

    更新日期:2002-10-01 00:00:00

  • Effects of oxygen concentrations on human fibroblasts treated with Fe(3+)-NTA.

    abstract::Free radicals derived from the reaction of iron and oxygen are thought to be one of the causes of tissue injury. In order to identify whether oxygen concentrations are an important factor in iron-mediated damage to cells, cytotoxic effects of Fe(3+)-NTA on human fibroblasts (KMST-6 line) were studied under the conditi...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:

    authors: Pu H,Sakaguchi M,Kondo T,Kondo A,Kawabata T,Namba M

    更新日期:2001-03-01 00:00:00

  • Highly frequent allelic loss of chromosome 6q16-23 in osteosarcoma: involvement of cyclin C in osteosarcoma.

    abstract::The molecular pathogenesis of osteosarcoma is very complicated and associated with chaotic abnormalities on many chromosomal arms. We analyzed 12 cases of osteosarcomas with comparative genomic hybridization (CGH) to identify chromosomal imbalances, and detected highly frequent chromosomal alterations in chromosome 6q...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:

    authors: Ohata N,Ito S,Yoshida A,Kunisada T,Numoto K,Jitsumori Y,Kanzaki H,Ozaki T,Shimizu K,Ouchida M

    更新日期:2006-12-01 00:00:00

  • Identification of two novel mutations of IRF6 in Korean families affected with Van der Woude syndrome.

    abstract::Van der Woude syndrome (VWS) is the most common autosomal dominant disorder with characteristic lip pits and clefts of the lip and/or palate (CL/P). The interferon regulatory factor 6 gene (IRF6) has been recently identified as the gene mutated in patients with VWS. Here, we report two novel mutations of IRF6 in two u...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:

    authors: Kim Y,Park JY,Lee TJ,Yoo HW

    更新日期:2003-10-01 00:00:00

  • Influence of interleukin-13 on beta-catenin levels in eosinophilic chronic rhinosinusitis cell culture.

    abstract::Chronic rhinosinusitis (CRS) is one of the most common chronic diseases. The etiology and classification of CRS, with and without nasal polyps, remain unclear. Eosinophils and their products are important in the pathophysiology of allergic diseases and in host immunity to certain organisms. Interleukin 13 (IL-13) play...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:

    authors: Sauter A,Stern-Straeter J,Chang RC,Hörmann K,Naim R

    更新日期:2008-04-01 00:00:00

  • miR‑93‑5p regulates the occurrence and development of esophageal carcinoma epithelial cells by targeting TGFβR2.

    abstract::Emerging studies have indicated that the dysregulation of microRNAs (miRNAs or miRs) plays a vital role in the development and metastasis of tumors. However, the role of miR‑93‑5p in esophageal carcinoma (EC) has not been extensively reported. The present study thus focused on the role of miR‑93‑5p and its downstream ...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2020.4836

    authors: Cai Y,Ruan W,Ding J,Wei N,Wang J,Zhang H,Ma N,Weng G,Su WK,Lin Y,Zhu K

    更新日期:2021-03-01 00:00:00

  • Downregulation of type I collagen expression in silibinin-treated human skin fibroblasts by blocking the activation of Smad2/3-dependent signaling pathways: potential therapeutic use in the chemoprevention of keloids.

    abstract::The inhibition of the Smad2/3 pathway is a key step involved in the downregulation of type I collagen synthesis, thus preventing keloid formation in tissue. In this study, we investigated the effect of silibinin on the proliferation of human skin fibroblasts (HSFs), as well as its effect on the expression of type I co...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2013.1303

    authors: Cho JW,Il KJ,Lee KS

    更新日期:2013-05-01 00:00:00

  • Troglitazone upregulates PTEN expression and induces the apoptosis of pulmonary artery smooth muscle cells under hypoxic conditions.

    abstract::The increased proliferation and decreased apoptosis of pulmonary artery smooth muscle cells (PASMCs) are the main causes of hypoxic pulmonary hypertension. In this study, we investigated the role of troglitazone [peroxisome proliferator-activated receptor γ (PPARγ) agonist] in the regulation of phosphatase and tensin ...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2013.1487

    authors: Pi WF,Guo XJ,Su LP,Xu WG

    更新日期:2013-11-01 00:00:00

  • Human chondrocytes differentially express matrix modulators during in vitro expansion for tissue engineering.

    abstract::Cartilage tissue engineering plays an important role in the generation of grafts for reconstructive surgery. In cultured chondrocytes, the dedifferentiation of cells seems unavoidable for multiplication. Dedifferentiated cells produce matrix of less quality, and the molecular basis is still not well understood. Theref...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:

    authors: Goessler UR,Bieback K,Bugert P,Naim R,Schafer C,Sadick H,Hormann K,Riedel F

    更新日期:2005-10-01 00:00:00

  • Pectin-enriched diet affects distribution and expression of apoptosis-cascade proteins in colonic crypts of dimethylhydrazine-treated rats.

    abstract::The colonic crypt contains highly proliferative cells in its base and differentiated cells on its luminal surface. Carcinogenesis significantly affects this orderly cellular distribution. The aims of this study were: i) to examine the expression of apoptosis-related proteins along the crypt-lumen axis during 1, 2-dime...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.6.6.689

    authors: Avivi-Green C,Madar Z,Schwartz B

    更新日期:2000-12-01 00:00:00

  • A new method for the quantification of aortic calcification by three-dimensional micro-computed tomography.

    abstract::To gain a better understanding of the mechanisms that underpin aortic calcification, rodent models have been previously utilised. Regions of calcium and phosphate deposition are commonly visualised using labor-intensive two-dimensional histomorphometric techniques. In this study, we developed a novel micro-computed to...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2013.1490

    authors: Huesa C,Millán JL,van 't Hof RJ,MacRae VE

    更新日期:2013-11-01 00:00:00

  • Ezrin, actin and cytoskeleton in apoptosis of esophageal epithelial cells induced by arsenic trioxide.

    abstract::Ezrin is a key protein in membrane-cytoskeleton interaction. Expression of ezrin in actin-rich cell surfaces may play a role in the modulation of cell shape and adhesion. The aim of this study was to detect ezrin, actin and cytoskeleton and to explore their relationship in the apoptosis of esophageal epithelial cells ...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:

    authors: Shen ZY,Xu LY,Li EM,Li JT,Chen MH,Shen J,Zeng Y

    更新日期:2003-09-01 00:00:00

  • Identification of sex hormone binding globulin-interacting proteins in the brain using phage display screening.

    abstract::The present study reports the identification of human sex hormone binding globulin (SHBG)-interacting proteins in the brain using a phage display-based screening technology. Phage display is a system in which a foreign protein is displayed on the surface of a bacteriophage as a fusion protein with one of the coat prot...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm_00000248

    authors: Gnanasekar M,Suleman FG,Ramaswamy K,Caldwell JD

    更新日期:2009-10-01 00:00:00

  • A peptide from Porphyra yezoensis stimulates the proliferation of IEC-6 cells by activating the insulin-like growth factor I receptor signaling pathway.

    abstract::Porphyra yezoensis (P. yezoensis) is the most noteworthy red alga and is mainly consumed in China, Japan and Korea. In the present study, the effects of a P. yezoensis peptide (PY‑PE) on cell proliferation and the associated signaling pathways were examined in IEC‑6 rat intestinal epithelial cells. First, the MTS assa...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2014.2037

    authors: Lee MK,Kim IH,Choi YH,Nam TJ

    更新日期:2015-02-01 00:00:00

  • Impact of combinatory growth factor application on rabbit Achilles tendon injury with operative versus conservative treatment: a pilot study.

    abstract::Acute Achilles tendon (AT) rupture is a common injury with a comparatively high complication rate. Presently, surgical treatments compete with nonoperative treatment modalities. The aim of this study was to elucidate the possible beneficial effects of short-term combinatory application of growth factors on tendon heal...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:

    authors: Konerding MA,Arlt F,Wellmann A,Li V,Li W

    更新日期:2010-02-01 00:00:00

  • Isolation of novel cell-penetrating peptides from a random peptide library using in vitro virus and their modifications.

    abstract::A number of cell-penetrating peptides (CPPs) have been reported, but their transduction efficiencies are too low to be used as intracellular carriers for therapeutic purposes. We conducted a comprehensive search to find novel CPPs using an in vitro virus (IVV) library, which presented random peptides consisting of 15 ...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:

    authors: Kamide K,Nakakubo H,Uno S,Fukamizu A

    更新日期:2010-01-01 00:00:00

  • Monoclonal TCR mRNA transcripts are preferentially detected in the TCR variable alpha chain in CD8(+) T-lymphocytes: implications for immunomonitoring.

    abstract::Clinical trials have started to implement tumor-associated antigens in the form of antigenic peptides in order to augment CD8(+) T-cell responses directed against autologous cancer cells. One of the surrogate markers for successful immunization is the characterization of T-lymphocytes reacting to the immunizing peptid...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.3.2.139

    authors: Höhn H,Reichert T,Neukirch C,Pilch H,Maeurer MJ

    更新日期:1999-02-01 00:00:00

  • Role of Rho kinase in lysophosphatidic acid-induced altering of blood-brain barrier permeability.

    abstract::Lysophosphatidic acid (LPA) the simplest of the water-soluble phospholipids, is produced by activated platelets, macrophage and endothelial cells. It also evokes various biological responses. When LPA concentrations reach high levels, brain injury, including stroke and intracerebral hemorrhage (ICH), occurs. Previous ...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2014.1618

    authors: Yu Y,Qin J,Liu M,Ruan Q,Li Y,Zhang Z

    更新日期:2014-03-01 00:00:00

  • Annexin A9 promotes invasion and metastasis of colorectal cancer and predicts poor prognosis.

    abstract::Annexin A9 (ANXA9), a member of annexin family, has been reported be associated with colorectal cancer (CRC) carcinogenesis. However, the clinical significance of ANXA9 in CRC, particularly its correlation to invasion and metastasis remains ambiguous. The aim of the present study was to investigate the significance of...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2018.3432

    authors: Yu S,Bian H,Gao X,Gui L

    更新日期:2018-04-01 00:00:00

  • [Corrigendum] Analysis of a nanoparticle‑enriched fraction of plasma reveals miRNA candidates for Down syndrome pathogenesis.

    abstract::After the publication of the above paper, the authors noted that the names of a couple of the authors listed on the paper were associated with the wrong affliation: Specifically, the eighth and ninth listed authors, Francesca Antonaros and Allison Piovesan, are located at DIMES at the University of Florence (fourth af...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章,已发布勘误

    doi:10.3892/ijmm.2019.4222

    authors: Salvi A,Vezzoli M,Busatto S,Paolini L,Faranda T,Abeni E,Caracausi M,Antonaros F,Piovesan A,Locatelli C,Cocchi G,Alvisi G,De Petro G,Ricotta D,Bergese P,Radeghieri A

    更新日期:2019-08-01 00:00:00

  • MicroRNA-4649-3p inhibits cell proliferation by targeting protein tyrosine phosphatase SHP-1 in nasopharyngeal carcinoma cells.

    abstract::The present study aimed to investigate the influence of microRNA-4649-3p on nasopharyngeal carcinoma (NPC) cell proliferation and how it regulated SHP-1 expression. The online software TargetScan was used to predict the microRNAs targeting SHP-1 and identified that miR-4649-3p was one of the possible miRNAs targeting ...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2015.2245

    authors: Pan X,Peng G,Liu S,Sun Z,Zou Z,Wu G

    更新日期:2015-08-01 00:00:00

  • Microarray analysis of insulin-regulated gene expression in the liver: the use of transgenic mice co-expressing insulin-siRNA and human IDE as an animal model.

    abstract::To characterize the changes in global gene expression in the livers of H1/siRNAinsulin-CMV/hIDE transgenic (Tg) mice in response to the reduced bioavailability of insulin, total RNA extracted from the livers of 20-week-old Tg and non-Tg mice was converted to cDNA, labeled with biotin and hybridized to oligonucleotide ...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:

    authors: Jee S,Hwang D,Seo S,Kim Y,Kim C,Kim B,Shim S,Lee S,Sin J,Bae C,Lee B,Jang M,Kim M,Yim S,Jang I,Cho J,Chae K

    更新日期:2007-12-01 00:00:00

  • Suppression of allergic and inflammatory responses by essential oils derived from herbal plants and citrus fruits.

    abstract::The aim of the present study was to investigate the biological activity of 20 essential oils (EOs) derived from herbal plants and citrus fruits. The in vitro anti-allergic and anti-inflammatory activities of these oils were investigated, and the EO which was found to have the strongest activity of the 20 EOs examined,...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2014.1720

    authors: Mitoshi M,Kuriyama I,Nakayama H,Miyazato H,Sugimoto K,Kobayashi Y,Jippo T,Kuramochi K,Yoshida H,Mizushina Y

    更新日期:2014-06-01 00:00:00

  • Personalized regulation of glioblastoma cancer stem cells based on biomedical technologies: From theory to experiment (Review).

    abstract::Glioblastoma multiforme (GBM) is one of the most aggressive brain tumors. GBM represents >50% of primary tumors of the nervous system and ~20% of intracranial neoplasms. Standard treatment involves surgery, radiation and chemotherapy. However, the prognosis of GBM is usually poor, with a median survival of 15 months. ...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章,评审

    doi:10.3892/ijmm.2018.3668

    authors: Bryukhovetskiy I,Ponomarenko A,Lyakhova I,Zaitsev S,Zayats Y,Korneyko M,Eliseikina M,Mischenko P,Shevchenko V,Shanker Sharma H,Sharma A,Khotimchenko Y

    更新日期:2018-08-01 00:00:00

  • Effects of different cellulose membranes regenerated from Styela clava tunics on wound healing.

    abstract::The aim of this study was to investigate the therapeutic effects of three different cellulose membranes (CMs) manufactured from Styela clava tunics (SCTs) on the healing of cutaneous wounds. We examined the physical properties and therapeutic effects of three CMs regenerated from SCTs (referred to as SCT‑ CMs), includ...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2017.2923

    authors: Song SH,Seong KY,Kim JE,Go J,Koh EK,Sung JE,Son HJ,Jung YJ,Kim HS,Hong JT,Hwang DY

    更新日期:2017-05-01 00:00:00

  • Cyclic stretch enhances bone morphogenetic protein-2-induced osteoblastic differentiation through the inhibition of Hey1.

    abstract::Substantial evidence has indicated that osteoblastic differentiation may be regulated by mechanical loads or bone morphogenetic protein-2 (BMP-2). BMP-2-induced in vivo osteogenesis can be significantly enhanced in the presence of mechanical stimuli, revealing the therapeutic potential of the combined application of B...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2015.2354

    authors: Zeng Z,Yin X,Zhang X,Jing D,Feng X

    更新日期:2015-11-01 00:00:00

  • SILAM for quantitative proteomics of liver Akt1/PKBα after burn injury.

    abstract::Akt1/protein kinase Bα (Akt1/PKBα) is a downstream mediator of the insulin signaling system. In this study we explored mechanism(s) for its role in burn injury. Akt1/PKBα in liver extracts from mice with burn injury fed with (2H7)-L-Leu was immunoprecipitated and isolated with SDS-PAGE. Two tryptic peptides, one in th...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2011.861

    authors: Lu XM,Tompkins RG,Fischman AJ

    更新日期:2012-03-01 00:00:00