Search results for "Wester"
showing 10 items of 1157 documents
Selectivity analysis of protein kinase CK2 inhibitors DMAT, TBB and resorufin in cisplatin-induced stress responses.
2009
Udgivelsesdato: 2009-Nov Targeting protein kinases as a therapeutic approach to treat various diseases, especially cancer is currently a fast growing business. Although many inhibitors are available, exhibiting remarkable potency, the major challenge is their selectivity. Here we show that the protein kinase CK2 inhibitors DMAT, TBB and resorufin differ in their selectivity against PI3K family members, since PI3K and DNA-PK are subject to inhibition by DMAT and TBB, however, not by resorufin. TBB and DMAT treatment together with cisplatin lead to an inhibition of cisplatin-induced stress signaling (as detected by phosphorylation of JNK and H2AX). In the case of resorufin no interference wit…
Artesunate derived from traditional Chinese medicine induces DNA damage and repair.
2008
Abstract Artesunate is a semisynthetic derivative from artemisinin, a natural product from the Chinese herb Artemisia annua L. It exerts antimalarial activity, and, additionally, artemisinin and its derivatives are active against cancer cells. The active moiety is an endoperoxide bridge. Its cleavage leads to the formation of reactive oxygen species and carbon-centered radicals. These highly reactive molecules target several proteins in Plasmodia, which is thought to result in killing of the microorganism. DNA damage induced by artemisinins has not yet been described. Here, we show that artesunate induces apoptosis and necrosis. It also induces DNA breakage in a dose-dependent manner as sho…
cIAP1 regulates TNF-mediated cdc42 activation and filopodia formation
2013
International audience; umour necrosis factor-α (TNF) is a cytokine endowed with multiple functions, depending on the cellular and environmental context. TNF receptor engagement induces the formation of a multimolecular complex including the TNFR-associated factor TRAF2, the receptor-interaction protein kinase RIP1 and the cellular inhibitor of apoptosis cIAP1, the latter being essential for NF-κB activation. Here, we show that cIAP1 also regulates TNF-induced actin cytoskeleton reorganization through a cdc42-dependent, NF-κB-independent pathway. Deletion of cIAP1 prevents TNF-induced filopodia and cdc42 activation. The expression of cIAP1 or its E3-ubiquitin ligase-defective mutant restore…
Expression of Hugl-1 is strongly reduced in malignant melanoma.
2005
The human gene Hugl-1 (Llgl/Lgl1) has significant homology to the Drosophila tumor suppressor gene lethal(2)giant larvae (lgl). The lgl gene codes for a cortical cytoskeleton protein, Lgl, that is involved in maintaining cell polarity and epithelial integrity. We speculate that Hugl-1 might play a role in epithelial-mesenchymal transition (EMT) and that loss of Hugl-1 expression plays a role in the development or progression of malignant melanoma. Thus, we evaluated melanoma cell lines and tissue samples of malignant melanoma for loss of Hugl-1 transcription. We found that Hugl-1 was downregulated or lost in all cell lines and in most of the tumor samples analysed, and that these losses wer…
Multivalent DR5 peptides activate the TRAIL death pathway and exert tumoricidal activity.
2010
Abstract Ongoing clinical trials are exploring anticancer approaches based on signaling by TRAIL, a ligand for the cell death receptors DR4 and DR5. In this study, we report on the selective apoptotic effects of multivalent DR5 binding peptides (TRAILmim/DR5) on cancer cells in vitro and in vivo. Surface plasmon resonance revealed up to several thousand-fold increased affinities of TRAILmim/DR5-receptor complexes on generation of divalent and trivalent molecules, the latter of which was achieved with a conformationally restricted adamantane core. Notably, only multivalent molecules triggered a substantial DR5-dependent apoptotic response in vitro. In tumor models derived from human embryoni…
Redistribution of CD95, DR4 and DR5 in rafts accounts for the synergistic toxicity of resveratrol and death receptor ligands in colon carcinoma cells.
2004
The natural phytoalexin resveratrol (3, 5, 4'-trihydroxystilbene) exhibits both chemopreventive and antitumor activities through a variety of mechanisms. We have shown previously that resveratrol-induced apoptosis of a human colon cancer cell line involved the redistribution of CD95 (Fas/Apo-1) into lipid rafts. Here, we show that, in colon cancer cells that resist to resveratrol-induced apoptosis, the polyphenol also induces a redistribution of death receptors into lipid rafts. This effect sensitizes these tumor cells to death receptor-mediated apoptosis. In resveratrol-treated cells, tumor necrosis factor (TNF), anti-CD95 antibodies and TNF-related apoptosis-inducing ligand (TRAIL) activa…
Hsp60 and Hsp10 down-regulation predicts bronchial epithelial carcinogenesis in smokers with chronic obstructive pulmonary disease.
2006
BACKGROUND. The relation between smoking, chronic obstructive pulmonary disease (COPD), and lung cancer (LC) is an open field of investigation. A higher frequency of adenocarcinoma has been reported in patients with COPD. Heat shock proteins (Hsps) are implicated in tumoral cell growth and differentiation. The aim of the present study was to investigate the expression of Hsp60 and Hsp10 in bronchial biopsies from smokers with COPD and in 10 lung cancer patients and to evaluate the association between Hsps expression and carcinogenetic steps of LC. METHODS. An immunohistochemical study was performed for Hsp60 and Hsp10 in bronchial biopsies from 35 COPD (postbronchodilator forced expiratory …
The expression of HSP60 and HSP10 in large bowel carcinomas with lymph node metastase
2005
Abstract Background The involvement of Heat Shock Proteins (HSP) in cancer development and progression is a widely debated topic. The objective of the present study was to evaluate the presence and expression of HSP60 and HSP10 in a series of large bowel carcinomas and locoregional lymph nodes with and without metastases. Methods 82 Astler and Coller's stage C2 colorectal cancers, of which 48 well-differentiated and 34 poorly-differentiated, were selected along with 661 lymph nodes, including 372 with metastases and 289 with reactive hyperplasia only, from the same tumours. Primitive tumours and both metastatic and reactive lymph nodes were studied; specifically, three different compartment…
Diorganotin(IV) and triorganotin(IV) complexes of meso-tetra(4-sulfonatophenyl) porphine induce apoptosis in A375 human melanoma cells
2006
The cytotoxic effect of several diorganotin(IV) and triorganotin(IV)-meso-tetra(4-sulfonatophenyl)porphine derivatives was tested and only the (Bu(2)Sn)(2)TPPS and the (Bu(3)Sn)(4)TPPS showed cytotoxicity on A375 human melanoma cells. To examine the pathway of (Bu(2)Sn)(2)TPPS or (Bu(3)Sn)(4)TPPS induced A375 cell death, DNA fragmentation analysis, Annexin V binding and PI uptake as well as caspases activation analysis by Western blot were carried out. A375 cells treated exhibited several typical characteristics of apoptosis. Both the (Bu(2)Sn)(2)TPPS and the (Bu(3)Sn)(4)TPPS compounds activate caspase-8 and caspase-9 leading to caspase-3 activation. Thus, we propose that these two porphiri…
In BCR-ABL-positive cells, STAT-5 tyrosine-phosphorylation integrates signals induced by imatinib mesylate and Ara-C.
2003
In BCR-ABL-positive cells, the transcription factor STAT-5 is constitutively activated by tyrosine phosphorylation. STAT-5 activation results in upregulation of bcl-X(L) and increased resistance to induction of apoptosis. Here, we investigated the effects of imatinib mesylate and cytosine arabinoside (Ara-C) on STAT-5 tyrosine-phosphorylation, cellular proliferation and induction of apoptosis in cell lines and primary hematopoietic cells. Imatinib mesylate treatment strongly suppressed STAT-5 tyrosine-phosphorylation in K562 and primary CML blasts. In contrast to JAK-2 and PI-3-kinase inhibition, exposure of K562 cells to imatinib mesylate resulted in obvious suppression of proliferation. R…