Abstract:
:Resistance of cancer cells to apoptosis is dependent on a balance of multiple genetic and epigenetic mechanisms, which up-regulate efficacy of the surviving growth factor-receptor signaling pathways and suppress death-receptor signaling pathways. The Insulin-like Growth Factor-1 Receptor (IGF-1R) signaling pathway is highly active in metastatic melanoma cells by mediating downstream activation of PI3K-AKT and MAPK pathways and controlling general cell survival and proliferation. In the present study, we used human melanoma lines with established genotypes that represented different phases of cancer development: radial-growth-phase WM35, vertical-growth-phase WM793, metastatic LU1205 and WM9 [1]. All these lines have normal NRAS. WM35, WM793, LU1205 and WM9 cells have mutated BRAF (V600E). WM35 and WM9 cells express normal PTEN, while in WM793 cells PTEN expression is down-regulated; finally, in LU1205 cells PTEN is inactivated by mutation. Cyclolignan picropodophyllin (PPP), a specific inhibitor of IGF-1R kinase activity, strongly down-regulated the basal levels of AKT activity in WM9 and in WM793 cells, modestly does so in LU1205, but has no effect on AKT activity in the early stage WM35 cells that are deficient in IGF-1R. In addition, PPP partially down-regulated the basal levels of active ERK1/2 in all lines used, highlighting the role of an alternative, non-BRAF pathway in MAPK activation. The final result of PPP treatment was an induction of apoptosis in WM793, WM9 and LU1205 melanoma cells. On the other hand, dose-dependent inhibition of IGF-1R kinase activity by PPP at a relatively narrow dose range (near 500 nM) has different effects on melanoma cells versus normal cells, inducing apoptosis in cancer cells and G2/M arrest of fibroblasts. To further enhance the pro-apoptotic effects of PPP on melanoma cells, we used a combined treatment of TNF-Related Apoptosis-Inducing Ligand (TRAIL) and PPP. This combination substantially increased death by apoptosis for WM793 and WM9 cells, but did so only modestly for LU1205 cells with very high basal activity of AKT. The ultimate goal of this direction of research is the discovery of a new treatment method for highly resistant human metastatic melanomas. Our findings provide the rationale for further preclinical evaluation of this novel treatment.
journal_name
Exp Cell Resjournal_title
Experimental cell researchauthors
Karasic TB,Hei TK,Ivanov VNdoi
10.1016/j.yexcr.2010.04.014subject
Has Abstractpub_date
2010-07-15 00:00:00pages
1994-2007issue
12eissn
0014-4827issn
1090-2422pii
S0014-4827(10)00182-5journal_volume
316pub_type
杂志文章abstract::Although periodontal diseases are initiated by bacteria that colonize the tooth surface and gingival sulcus, the host response is believed to play an essential role in the breakdown of connective tissue and bone. Mitochondrial reactive oxygen species (mtROS) have been proposed to regulate the activation of the inflamm...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2016.08.007
更新日期:2016-09-10 00:00:00
abstract::Gallbladder cancer (GBC) is an aggressive malignancy of the bile duct, which is associated with a low (5-year) survival and poor prognosis. The transcription factor HIF-1α is implicated in the angiogenesis, cell survival, epithelial mesenchymal transition (EMT) and invasiveness of GBC. In this study, we have investiga...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2014.11.021
更新日期:2015-03-15 00:00:00
abstract::Spinal muscular atrophy (SMA), a recessive, neuromuscular disease, is caused by a mutation or deletion in the SMN1 gene. The SMN2 gene is present in the same region of chromosome 5 and is similar in DNA sequence to SMN1 except for a T at position +6 of exon 7 that is likely the predominant functional difference betwee...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2007.10.012
更新日期:2008-02-15 00:00:00
abstract::Keratinocytes in human skin undergo apoptosis during various inflammatory processes and after ultraviolet (UV) irradiation. To determine if keratinocyte apoptosis may be mediated by the Fas/APO-1 receptor (CD95), a signal transduction pathway known to initiate programmed cell death of lymphocytes, we investigated Fas ...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.1997.3514
更新日期:1997-05-01 00:00:00
abstract::Neuroblastoma is a childhood tumor with a poor survival in advanced stage disease despite intensive chemotherapeutic regimes. The new histone deacetylase (HDAC) inhibitor BL1521 has shown promising results in neuroblastoma. Inhibition of HDAC resulted in a decrease in proliferation and metabolic activity, induction of...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2005.06.024
更新日期:2005-10-01 00:00:00
abstract::Heme has been reported to exert a control over its own biosynthesis and to affect the erythroid differentiation process at different sites. In this study, succinylacetone, a powerful inhibitor of delta-aminolevulinic acid dehydrase was used to block heme synthesis and to study the effects of heme depletion on the dime...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/0014-4827(84)90171-x
更新日期:1984-10-01 00:00:00
abstract::CEACAM1-4S (carcinoembryonic antigen-related cell adhesion molecule 1) is a type I membrane protein with a short (12-amino acid) cytoplasmic tail. Wild type CEACAM1-4S-transfected MCF7 cells form glands with lumena when grown in 3D culture, while null mutations of two putative phosphorylation sites (T457A and S459A) i...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2009.11.001
更新日期:2010-02-15 00:00:00
abstract::Primary cultures of renal rabbit proximal tubule cells were initiated from a pure suspension of proximal tubule fragments. Proximal tubule cells were grown in a hormone-supplemented, serum-free medium containing low concentrations of antibiotics. Confluent monolayers exhibited multicellular dome formation, indicating ...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/0014-4827(91)90123-c
更新日期:1991-05-01 00:00:00
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journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2010.08.010
更新日期:2011-01-01 00:00:00
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journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2005.08.022
更新日期:2005-11-15 00:00:00
abstract::Cancer stem cells (CSCs) are a subpopulation of chemoresistant cells that play a critical role in disease recurrence following chemotherapy. It has been reported that microRNA-133b (miR-133b) acts as a tumor suppressor in colorectal cancer (CRC). However, whether miR-133b is associated with CRC stemness and chemoresis...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2019.111597
更新日期:2019-12-01 00:00:00
abstract::Treatment with ionic detergents of nuclei isolated from various continuously growing cell lines generally yields chromatin samples of high viscosity. Extensive treatment with nuclease-free proteinase K or pronase solubilized the viscous lysates with > 90% of the DNA migrating at approximately 50 kb. Freshly prepared h...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.1995.1381
更新日期:1995-12-01 00:00:00
abstract::The cancer cells residing in the hypoxic layer are resistant to radiation and these are ones responsible for cancer recurrence after radiation therapy. One of the reasons why hypoxic cancer cells acquire radioresistance may be attributable to changes in the gene expression profile by the activation of hypoxia inducibl...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2015.03.009
更新日期:2015-05-01 00:00:00
abstract::Oligomerization of Fas receptor by its ligand, FasL, activates a signaling cascade that leads to apoptosis of Fas bearing cells. Interestingly, many epithelia coexpress Fas and FasL, yet FasL does not trigger Fas present on the same or neighboring cells to induce spontaneous apoptosis. Here, we show that Fas and FasL ...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/s0014-4827(02)00056-3
更新日期:2003-04-01 00:00:00
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journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2018.10.008
更新日期:2019-01-01 00:00:00
abstract::Experiments are described which show that the torsional oscillations arising in a strand of the slime mould, Physarum polycephalum, under certain conditions remain closely correlated to oscillations in cytoplasmic streaming. When this is the case, the direction of rotation is related to the direction of streaming by a...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/0014-4827(83)90401-9
更新日期:1983-11-01 00:00:00
abstract::Chronic lymphocytic leukemia (CLL) results from the uncontrolled proliferation and accumulation of B-1 cells, many of which demonstrate self-reactivity. The response of B-1 cells to mitogen after undergoing malignant transformation is still unclear. Using our established malignant B-1 cell lines derived from the NZB m...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.2000.5122
更新日期:2001-04-01 00:00:00
abstract:BACKGROUND:CDK8 is associated with the transcriptional Mediator complex and has been shown to regulate several transcription factors implicated in cancer. As a pancreatic cancer oncogene, the role of CDK8 in cancer angiogenesis remains unclear. Here, we investigated the contribution of CDK8 in pancreatic cancer angioge...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2018.05.033
更新日期:2018-08-15 00:00:00
abstract::SIRT5 has a wide range of functions in different cellular processes such as glycolysis, TCA cycle and antioxidant defense, which mediates lysine desuccinylation, deglutarylation and demalonylation. Recent evidences have implicated that SIRT5 is a potential suppressor of gastric cancer (GC). However, the underlying mec...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2019.06.028
更新日期:2019-09-15 00:00:00
abstract::Matrix metalloproteinases (MMPs) play a key role in cellular invasion and growth. Recent observations on tumor tissue samples suggest that MMP activity is altered in relation to cell density. Therefore, we examined MMP(-1,-2,-3,-8,-9,-10,-11 and -13) and TIMP-1/-2 expression of well-defined cell densities in breast ca...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2004.12.019
更新日期:2005-04-15 00:00:00
abstract::Accumulating evidence has suggested that thyroid hormone receptor interacting protein 6 (TRIP6) is a novel tumor-related regulator that is aberrantly expressed in multiple tumors and contributes to tumor progression and metastasis. Yet, little is known about the role of TRIP6 in cervical cancer. In the current study, ...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2020.112248
更新日期:2020-11-01 00:00:00
abstract::The role of the F-actin cytoskeleton in cell volume regulation was studied in Ehrlich ascites tumor cells, using a quantitative rhodamine-phalloidin assay, confocal laser scanning microscopy, and electronic cell sizing. A hypotonic challenge (160 mOsm) was associated with a decrease in cellular F-actin content at 1 an...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.1999.4615
更新日期:1999-10-10 00:00:00
abstract::A monoclonal antibody raised against microtubule-associated protein-1 (MAP-1) binds to nuclei of normal human fibroblasts, its binding site being detected as intranuclear immunofluorescent dots. The percentage of cells showing these dots increased with insulin, hydrocortisone, epidermal growth factor (EGF), and transf...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/0014-4827(85)90480-x
更新日期:1985-06-01 00:00:00
abstract::Autophagy is an intracellular degradation pathway that is highly conserved during the evolution of eukaryotes and is based on lysosome. Under nutritional deficiencies or stress, cells can clear damaged and necrotic organelles and proteins through autophagy to maintain the homeostasis of cells and organisms. Studies ha...
journal_title:Experimental cell research
pub_type: 杂志文章,评审
doi:10.1016/j.yexcr.2020.111925
更新日期:2020-04-15 00:00:00
abstract::The histone 2A variant macroH2A1.2 is expressed in female and male mammals and is implicated in X-chromosome inactivation and autosomal gene silencing. In undifferentiated and early differentiating murine embryonic stem (ES) cells a cytosolic pool of macroH2A1.2 has recently been reported and found to be associated wi...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.2001.5277
更新日期:2001-08-15 00:00:00
abstract::In preceding studies, the IP3-sensitive Ca2+ store of the hamster insulinoma cell line, HIT, was detected in cell surface protrusions such as microvilli and related membrane structures [Lange, K., and Brandt, U. (1993) FEBS Lett. 320, 183-188; and (1993) FEBS Lett. 325, 205-209]. In this study, these experiments were ...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.1996.0316
更新日期:1996-11-01 00:00:00
abstract::Tetracyclines have long been used as valuable broad-spectrum antibiotics. The high antibacterial activity of tetracyclines, combined with their good tolerability, has led to their widespread use in treating various infectious diseases. However, similar to other antibiotics, tetracyclines are also known for their adver...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2013.11.012
更新日期:2014-01-15 00:00:00
abstract::When exponentially growing NHIK 3025 cells were shifted from medium containing 30% serum to medium containing 0.03% serum the rate of net protein accumulation was reduced due to both a reduction in the rate of protein synthesis and an increase in the rate of protein degradation. This change in growth conditions increa...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/0014-4827(84)90788-2
更新日期:1984-11-01 00:00:00
abstract::Using L1210 murine leukemia cells, we have previously shown that in response to treatment with drugs having different targets, apoptotic cell death occurs through at least two different signaling pathways. Here, we present evidence that nuclear extracts from staurosporine-treated cells elicit DNase II activity that is...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.1999.4737
更新日期:2000-01-10 00:00:00
abstract::In human peripheral blood mononuclear cells, ciliary neurotrophic factor (CNTF) weakly suppressed endotoxin-induced interleukin (IL)-1 and prostaglandin E2(PGE2). Suppression of PGE2 and IL-8 synthesis was significantly greater (up to 42.6%, P < 0.05) by adding a 10-fold molar excess of soluble CNTF receptor (sCNTFR a...
journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.1994.1313
更新日期:1994-11-01 00:00:00