Abstract:
:We recently reported that LY294002 (LY29) and LY303511 (LY30) sensitized tumor cells to drug-induced apoptosis independent of the phosphoinositide 3-kinase/Akt pathway. Here, we investigated the mechanism of LY30-induced sensitization of human neuroblastoma cells to TRAIL-mediated apoptosis. We provide evidence that LY30-induced increase in intracellular H(2)O(2) up-regulates the expression of TRAIL receptors (DR4 and DR5) in SHEP-1 cells by activating mitogen-activated protein kinases, resulting in a significant amplification of TRAIL-mediated caspase-8 processing and activity, cytosolic translocation of cytochrome c, and cell death. Involvement of the death receptors was further confirmed by the ability of blocking antibodies against DR4 and/or DR5 to inhibit LY30-induced TRAIL sensitization. Pharmacologic inhibition of c-Jun NH(2) terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) activation by SP600125 and PD98059, respectively, blocked LY30-induced increase in sensitization to TRAIL-mediated death. Finally, small interfering RNA-mediated gene silencing of JNK and ERK inhibited LY30-induced increase in surface expression of DR4 and DR5, respectively. These data show that JNK and ERK are two crucial players involved in H(2)O(2)-mediated increase in TRAIL sensitization of tumor cells upon exposure to LY30 and underscore a novel mode of action of this inactive analogue of LY29. Our findings could have implications for the use of LY30 and similar compounds for enhancing the apoptotic sensitivity of neuroblastoma cells that often become refractory to chemotherapy.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Shenoy K,Wu Y,Pervaiz Sdoi
10.1158/0008-5472.CAN-08-1996subject
Has Abstractpub_date
2009-03-01 00:00:00pages
1941-50issue
5eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-08-1996journal_volume
69pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::Tyrosine phosphorylation (pTyr) plays a pivotal role in signal transduction and is commonly dysregulated in cancer. As a result, profiling tumor pTyr levels may reveal therapeutic insights critical to combating disease. Existing discovery and targeted mass spectrometry-based methods used to monitor pTyr networks invol...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-20-3804
更新日期:2021-01-28 00:00:00
abstract::Pleiotropic resistance to rhodamine 123 (Rho-123) in Adriamycin (ADM)-resistant Friend leukemia cells was circumvented by cotreatment with 10 microM verapamil. Increased cytotoxicity corresponded to higher intracellular Rho-123 levels. The verapamil-induced increase of drug accumulation in resistant cells is accounted...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-06-01 00:00:00
abstract::There is considerable evidence that sphingosine kinases play a key role in cancer progression, which might involve positive selection of cancer cells that have been provided with a survival and growth advantage as a consequence of overexpression of the enzyme. Therefore, inhibitors of sphingosine kinase represent a no...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:10.1158/0008-5472.CAN-11-2364
更新日期:2011-11-01 00:00:00
abstract::Levels of epidermal growth factor receptor (EGF-R) and insulin-like growth factor receptor (IGF-R) in breast cancer tissue were evaluated. The binding of growth factors was compared to the content of estrogen receptors (ER) and progesterone receptors (PgR). EGF-R correlated negatively to the ER and PgR (Kendall correl...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-03-01 00:00:00
abstract::Pheophorbide a (PhA), a chlorophyll catabolite, was shown to be an ABCG2 substrate based on Abcg2(-/-) knockout mouse studies (J. W. Jonker et al., Proc. Natl. Acad. Sci. USA, 99: 15649-15654, 2002). We developed a functional assay for ABCG2 using PhA and the ABCG2 inhibitor fumitremorgin C. In selected cell lines exp...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.can-03-3298
更新日期:2004-02-15 00:00:00
abstract::Protein synthesis is a vital cellular process that regulates growth and metabolism. It is controlled via signaling networks in response to environmental changes, including the presence of nutrients, mitogens, or starvation. The phosphorylation state of proteins involved in translation initiation is a limiting factor t...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:10.1158/0008-5472.CAN-12-0026
更新日期:2012-08-15 00:00:00
abstract::Solid tumors contain a subset of stem-like cells that are resistant to the cytotoxic effects of chemotherapy/radiotherapy, but their susceptibility to cytolytic T lymphocyte (CTL) effector mechanisms has not been well characterized. Using a panel of early-passage human brain tumor stem/initiating cell (BTSC) lines der...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-09-2687
更新日期:2009-12-01 00:00:00
abstract::Promotional properties of a high-fat diet in intestinal cancer were studied by feeding a 30% beef fat diet to 8 groups of rats (25 rats/group) for time periods varying from 1 to 21 weeks after 8 weekly s.c. injections of azoxymethane (AOM) (8 mg/ kg). Two other groups were fed the high-fat diet, one for 8 weeks prior ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1979-12-01 00:00:00
abstract::TGF-β has limited effects on ovarian cancer cells, but its contributions to ovarian tumor growth might be mediated through elements of the tumor microenvironment. In the present study, we tested the hypothesis that TGF modulates ovarian cancer progression by modulating the contribution of cancer-associated fibroblasts...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-13-0023
更新日期:2013-08-15 00:00:00
abstract::Human mammary and other carcinoma cells secrete and express on their cell surfaces complex, mucin-like glycoproteins (Mr greater than 10(6] that are recognized as tumor-associated antigens by a variety of monoclonal antibodies (MAbs). One such MAb, B72.3, has been extensively studied as to range of reactivity for a va...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-12-01 00:00:00
abstract::Previous studies have indicated that an autostimulatory transforming growth factor was required for the optimal growth of SW-13 adrenal carcinoma cells in soft agar. The production of SW-13 colony-stimulating activity by other human malignant cell lines of both epithelial and mesenchymal origin has been demonstrated. ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-09-01 00:00:00
abstract::Anticancer drug resistance results from selective pressure of chemotherapy, together with mutations or epigenetic changes that make cells refractory to treatment. In cancer cells, we report that gene expression associated with vesicle shedding correlates with chemosensitivity profiles. Experiments with doxorubicin and...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-08-01 00:00:00
abstract::Hepatocellular carcinoma (HCC) was thought historically to arise from hepatocytes, but gene expression studies have suggested that it can also arise from fetal progenitor cells or their adult progenitor progeny. Here, we report the identification of a unique population of fetal liver progenitor cells in mice that can ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-13-3275
更新日期:2014-08-15 00:00:00
abstract::The pharmacodynamic parameters of 1-beta-D-arabinofuranosylcytosine (ara-C) in patient plasma and its active anabolite 1-beta-D-arabinofuranosylcytosine-5-triphosphate (ara-CTP) in circulating and bone marrow blast cells were studied in 20 pediatric patients with acute leukemia. ara-C (3 g/m2) was administered as a sh...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-12-15 00:00:00
abstract::Drugs that affect blood flow have been shown to be whole body radiation protectors. Using NG-nitro-L-arginine, a specific inhibitor of nitric oxide synthase, and the NO-releasing agent (C2H5)2N[N(O)NO-]Na+ (DEA/NO), we have studied the ability of NO to modulate whole body radiation toxicity in C3H mice. NG-Nitro-L-arg...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1994-07-01 00:00:00
abstract::It has been postulated that the intestinal anaerobes play a role in the etiology of large bowel cancer. This study was designed to characterize and compare the fecal anaerobes of patients with large bowel cancer, patients with nonhereditary large bowel polyps, and healthy control subjects. Although some distributional...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1978-12-01 00:00:00
abstract::Inflammation affects tumor immune surveillance and resistance to therapy. Here, we show that production of IL1β in primary breast cancer tumors is linked with advanced disease and originates from tumor-infiltrating CD11c+ myeloid cells. IL1β production is triggered by cancer cell membrane-derived TGFβ. Neutralizing TG...
journal_title:Cancer research
pub_type: 临床试验,杂志文章
doi:10.1158/0008-5472.CAN-18-0413
更新日期:2018-09-15 00:00:00
abstract::The WWOX (WW domain containing oxidoreductase) gene was recently identified as a candidate tumor suppressor gene at 16q23.3-24.1, a chromosome region that spans the common fragile site FRA16D. To evaluate the potential role of the WWOX gene in esophageal squamous cell carcinomas, we examined 36 tumors for genetic alte...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2002-04-15 00:00:00
abstract::Phosphoglucose isomerase (PGI) is a multifunctional enzyme that functions in glucose metabolism as a glycolytic enzyme catalyzing an interconversion between glucose and fructose inside the cell, while it acts as cytokine outside the cell, with properties that include autocrine motility factor (AMF)-regulating tumor ce...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-09-3880
更新日期:2010-11-15 00:00:00
abstract::Inherited mutations of the human BRCA2 gene confer increased risks for developing breast, ovarian, and several other cancers. Unlike previously described Brca2 knockout mice that display predominantly embryonic lethal phenotypes, we developed mice with a homozygous germ-line deletion of Brca2 exon 27 that exhibit a mo...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2002-02-15 00:00:00
abstract::I have attempted to illustrate the many different properties of retroviruses and their presence in a wide variety of animal species including humans. Since the turn of this century, progress in the field of retrovirology has been noteworthy and many new and important scientific observations have been made (Table 7). A...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:
更新日期:1986-11-01 00:00:00
abstract::The anticancer effects of red wine have attracted considerable attention. Resveratrol (3,5,4'-trihydroxy-trans -stilbene) is a well-known polyphenolic compound of red wine with cancer chemopreventive activity. However, the basis for this activity is unclear. We studied leukotriene A(4) hydrolase (LTA(4)H) as a relevan...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-10-2858
更新日期:2010-12-01 00:00:00
abstract::The high uptake and prolonged renal retention of monoclonal antibody fragments that are conjugated with radiometal chelates precludes their routine clinical use due to high background counts, which may hinder detection of nearby lesions and/or cause renal radiotoxicity. We report on the potential use of Lys as a pharm...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-11-15 00:00:00
abstract::The genetic status of cyclin genes was examined in a panel of 47 colorectal carcinoma cell lines. Cyclin D2 was found to be amplified in one tumor and cyclin E in another. In each of the two cases, the amplified cyclin gene was overexpressed at the protein or mRNA level. Cyclin D1, previously shown to be amplified in ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-05-01 00:00:00
abstract::1-Nitropyrene, a direct-acting mutagenic component of extracts of diesel exhaust and ambient air particulates, is one of the major nitroarenes found in products of incomplete combustion. Injection of this compound into newborn Sprague-Dawley-derived CD rats at 100 mumol/kg body weight s.c. once a week for 8 weeks indu...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-03-01 00:00:00
abstract::Cutaneous melanomas have been found to express several immunogenic differentiation melanoma-associated antigens (MAAs) that have been suggested to play an important role in disease outcome. Adaptive host immunity to MAAs has shown some level of control on melanoma progression. To date, there has been no definitive rep...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-01-15 00:00:00
abstract::The calcium channel blocker verapamil has been shown to reverse multidrug resistance (T. Tsuruo et al., Cancer Res. 41: 1967-1972, 1981), but the mechanism of action of this agent has not been fully elucidated. A radioactive photoactive analogue of verapamil, N-[benzoyl-3,5-3H-(+/-)-5-[(3,4-dimethoxyphenetyl)methylami...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-09-15 00:00:00
abstract::Deleterious mutations of the ubiquitin carboxy-terminal hydrolase BAP1 found in cancers are predicted to encode inactive truncated proteins, suggesting that loss of enzyme function is a primary tumorigenic mechanism. However, many tumors exhibit missense mutations or in-frame deletions or insertions, often outside the...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-17-2876
更新日期:2018-03-01 00:00:00
abstract::TuAg.1 is a tumor-associated membrane glycoprotein first identified in rat hepatocellular carcinoma by monoclonal antibodies (mAbs) 324.5 and 324.9. This oncofetal antigen is also expressed by hepatocytes in cell culture but not normal adult hepatocytes in vivo. Affinity chromatography and preparative continuous eluti...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-09-01 00:00:00
abstract::PR-104, currently in phase II clinical trials, is a phosphate ester pre-prodrug which is converted in vivo to its cognate alcohol, PR-104A, a prodrug designed to exploit tumor hypoxia. Bioactivation occurs via one-electron reduction to DNA crosslinking metabolites in the absence of oxygen. However, certain tumor cell ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-09-3237
更新日期:2010-02-15 00:00:00