Abstract：
:Elevated oxidative stress is observed more frequently in cancer cells than in normal cells. It is therefore expected that additional exposure to a low level of reactive oxygen species (ROS) will push cancer cells toward death, whereas normal cells might maintain redox homeostasis through adaptive antioxidant responses. We previously showed that parthenolide enhances ROS production in prostate cancer cells through activation of NADPH oxidase. The present study identifies KEAP1 as the downstream redox target that contributes to parthenolide's radiosensitization effect in prostate cancer cells. In vivo, parthenolide increases radiosensitivity of mouse xenograft tumors but protects normal prostate and bladder tissues against radiation-induced injury. Mechanistically, parthenolide increases the level of cellular ROS and causes oxidation of thioredoxin (TrX) in prostate cancer cells, leading to a TrX-dependent increase in a reduced state of KEAP1, which in turn leads to KEAP1-mediated PGAM5 and Bcl-xL (BCL2L1) degradation. In contrast, parthenolide increases oxidation of KEAP1 in normal prostate epithelial cells, leading to increased Nrf2 (NFE2L2) levels and subsequent Nrf2-dependent expression of antioxidant enzymes. These results reveal a novel redox-mediated modification of KEAP1 in controlling the differential effect of parthenolide on tumor and normal cell radiosensitivity. Furthermore, they show it is possible to develop a tumor-specific radiosensitizing agent with radioprotective properties in normal cells.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Xu Y,Fang F,Miriyala S,Crooks PA,Oberley TD,Chaiswing L,Noel T,Holley AK,Zhao Y,Kiningham KK,Clair DK,Clair WHdoi
10.1158/0008-5472.CAN-12-4297subject
Has Abstractpub_date
2013-07-15 00:00:00pages
4406-17issue
14eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-12-4297journal_volume
73pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract：:Signaling through the insulin-like growth factor-I receptor (IGF-IR) is implicated in cellular proliferation, apoptosis, carcinogenesis, metastasis, and resistance to cytotoxic cancer therapies. Targeted disruption of IGF-IR signaling combined with cytotoxic therapy may therefore yield improved anticancer efficacy ove...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-06-2000
更新日期：2007-02-01 00:00:00
abstract：:A truncating allele of the cell cycle checkpoint kinase CHK2 is present in 1% of the population, conferring a moderate increase in breast cancer risk, and inactivation of chk2 enhances mammary tumorigenesis in mice with targeted inactivation of brca1. We used the mouse mammary tumor virus (MMTV) promoter to target exp...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-05-1237
更新日期：2006-02-15 00:00:00
abstract：:An androgen-dependent tumor (SCC8 tumor) was obtained by inoculating an androgen-responsive cell line derived from the androgen-responsive Shionogi carcinoma 115 (SC115) into mice and then treating the mice with testosterone propionate (TP) at a pharmacological dose (400 micrograms/day). The SCC8 tumor differed in his...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1989-02-01 00:00:00
abstract：:Clear cell renal carcinomas are most frequently characterized by loss of function of both copies of the von Hippel-Lindau (VHL) disease gene, suggesting that the VHL gene product plays an important role in regulating renal cell proliferation. To directly assess the function of the VHL gene product, we transfected the ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1995-11-01 00:00:00
abstract：:Cells deficient in DNA polymerase beta (beta-pol) are impaired in base excision repair (BER) and hypersensitive to various DNA damaging agents, including methylating mutagens. Hypersensitivity of beta-pol-deficient cells to methylating agents is because of induction of apoptosis (Ochs et al., Cancer Res., 59: 1544-155...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2002-03-01 00:00:00
abstract：:"Self" melanocyte differentiation antigens are potential targets for specific melanoma immunotherapy. Vaccination against murine tyrosinase-related protein (TRP)-1/gp75 was shown recently to cause melanoma rejection, which was accompanied by autoimmune skin depigmentation (vitiligo). To further explore the linkage bet...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2000-01-15 00:00:00
abstract：:The genetic and epigenetic effects of nutritional folate deficiency were studied in two Chinese hamster ovary (CHO) cell lines. The CHO-AA8 cell line (hemizygous at the aprt locus) and CHO-UV5 (DNA repair-deficient mutant of AA8) were cultured in Ham's F-12 medium or in custom-prepared Ham's F-12 medium lacking folic ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1994-10-01 00:00:00
abstract：:The clinical management of cutaneous melanoma would benefit significantly from a better understanding of the molecular changes that occur during melanocytic progression to a melanoma phenotype. To gain unique insights into this process, we developed a three-dimensional in vitro model that allows observations of normal...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-05-2497
更新日期：2005-11-15 00:00:00
abstract：:The thymidylate synthase reaction remains an important target for widely used anticancer agents; however, the clinical utility of these drugs is limited by the occurrence of cellular resistance. Despite the considerable amount of information available regarding mechanisms of drug action, the relative significance of d...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2002-09-01 00:00:00
abstract：:The possible influence of phenobarbital and phenytoin treatment on cancer risk was investigated in a case-control study nested in a cohort of 8004 epileptic patients in Denmark. Information on anticonvulsive treatments was abstracted for 95% of 60 patients with cancers of the liver and biliary tract or malignant lymph...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1995-01-15 00:00:00
abstract：:A previous study demonstrated inhibition of growth of primary rat mammary carcinomas after infusion of tumor-bearer plasma absorbed against Sepharose derivatives. In this report we have quantitated changes in individual complement components that occur during absorption of rat plasma with Sepharose derivatives and def...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1985-09-01 00:00:00
abstract：:The simultaneous distribution of monoclonal 131I-labeled anti-carcinoembryonic antigen (CEA) immunoglobulin (IgG) (NP-2) or 131I-labeled irrelevant myeloma IgG (Ag8) and [3H]thymidine was studied in hamsters bearing transplants of the GW-39 human colon carcinoma by qualitative double-tracer whole-body autoradiography....
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1987-04-15 00:00:00
abstract：:Tumor resistance to cytotoxic drugs is one of the main obstacles to successful cancer therapy. Emerging evidence suggests that chemoresistance is promoted by substances released from dead and damaged cells that activate the host repair program orchestrated by Toll-like receptor-4 (TLR4). TLR4 is often overexpressed in...
journal_title：Cancer research
pub_type： 杂志文章,评审
doi：10.1158/0008-5472.CAN-14-3525
更新日期：2015-06-15 00:00:00
abstract：:The growth of human melanoma cells FO-1 in nude mice is strongly inhibited or even abrogated when the cells are stably transfected with a plasmid expressing an antisense RNA to the insulin-like growth factor 1 receptor (IGF-1R) RNA, which causes a marked reduction in the number of IGF-1 receptors. When a tumor arises ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1994-09-15 00:00:00
abstract：:Oncogenic BRAF alleles are both necessary and sufficient for cellular transformation, suggesting that chemical inhibition of the activated mutant protein kinase may reverse the tumor phenotype. Here, we report the characterization of SB-590885, a novel triarylimidazole that selectively inhibits Raf kinases with more p...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-06-2554
更新日期：2006-12-01 00:00:00
abstract：:The cytotoxic activity against human tumor cells of toxic conjugates of Pseudomonas exotoxin with anti-transferrin receptor antibody or epidermal growth factor was potentiated up to 10 to 20-fold by the calcium antagonists verapamil, D-600, and diltiazem and by the lysosomotropic agent beta-glycylphenyl-naphthylamide....
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1985-03-01 00:00:00
abstract：:In human breast carcinomas, increased copy number of DNA sequences derived from the long arm of chromosome 20 (20q) has been commonly observed by both chromosome microdissection and comparative genomic hybridization. This chromosomal region is likely to contain one or more genes that are the biological targets of this...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1996-08-01 00:00:00
abstract：:The Notch signaling pathway is required in both nonneoplastic neural stem cells and embryonal brain tumors, such as medulloblastoma, which are derived from such cells. We investigated the effects of Notch pathway inhibition on medulloblastoma growth using pharmacologic inhibitors of gamma-secretase. Notch blockade sup...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-06-0858
更新日期：2006-08-01 00:00:00
abstract：:The LNCaP cell line was established from a metastatic lesion of human prostatic adenocarcinoma. The LNCaP cells grow readily in vitro (up to 8 x 10(5) cells/sq cm; doubling time, 60 hr), form clones in semisolid media, are highly resistant to human fibroblast interferon, and show an aneuploid (modal number, 76 to 91) ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1983-04-01 00:00:00
abstract：:Pleural fluid from a child previously treated for rhabdomyosarcoma produced colonies in vitro. Cells from these colonies appeared to have the light and electron microscopic appearance of rhabdomyosarcoma cells. In this case, the malignant nature of the effusion had been suspected because of the patient's previous hist...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1975-07-01 00:00:00
abstract：:HOXA genes encode critical transcriptional regulators of embryonic development that have been implicated in cancer. In this study, we documented functional relevance and mechanism of activation of HOXA9 in glioblastoma (GBM), the most common malignant brain tumor. Expression of HOXA genes was investigated using revers...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-09-2189
更新日期：2010-01-15 00:00:00
abstract：:Heterotopic new bone formation was induced by implanting pieces of demineralized bone matrix in the abdominal wall of 22 growing Sprague-Dawley rats. The animals were divided into three groups and were given, 24 hr after initiation of the bone induction process, a single i.v. injection of methotrexate, 100 or 250 mg/k...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1984-04-01 00:00:00
abstract：:The antitumor effects of methotrexate with 5-fluorouracil against the Sarcoma 180 mouse tumor model were found to be schedule dependent. Pretreatment of tumor-bearing animals with methotrexate significantly enhanced the antitumor activity of the combination relative to simultaneous treatment or to those with methotrex...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1977-01-01 00:00:00
abstract：:A variety of heterologous mammalian cells were inoculated into nude mice and scored for tumorigenicity. The cells tested were from primary cell cultures, established cell lines of neoplastic origin, established cell lines of nontumor origin, and primary cell cultures transformed by oncogenic viruses. Regardless of the...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1976-04-01 00:00:00
abstract：:Malignant pleural mesothelioma (MPM) is an aggressive malignant tumor that secretes various angiogenic factors. The main inhibitor of plasminogen activators, PAI-1 (SERPINE1), has been implicated in tumor progression and angiogenesis, and high PAI-1 expression has been associated with poor prognosis in MPM patients. I...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-15-1796
更新日期：2016-06-01 00:00:00
abstract：:Many but not all of the cell surface antigens studied were released into tissue culture medium of human colorectal carcinoma and melanoma cells maintained in vitro. Two groups of monoclonal antibody-defined antigens are described. One group is composed of molecules that are released easily and in large quantitites int...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1981-07-01 00:00:00
abstract：:Monoclonal antibody HT462 recognizes a human T-cell leukemia virus type I (HTLV-I)-associated Mr 52,000 glycoprotein (HA-gp52), which is found on the surface of HTLV-infected cells. Whether HA-gp52 is encoded by the virus or by the infected cells has not yet been established. Using monoclonal HT462 in a competitive bi...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1985-07-01 00:00:00
abstract：:Previous work in our laboratory has demonstrated that antisera to proteins found in the urine of bladder cancer patients can distinguish between urine samples from these patients and those from normal individuals when tested by a complement-fixation assay. Antisera which were reactive with individual tumor-associated ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1982-07-01 00:00:00
abstract：:We have found that the synthetic compound CC-5079 potently inhibits cancer cell growth in vitro and in vivo by a novel combination of molecular mechanisms. CC-5079 inhibits proliferation of cancer cell lines from various organs and tissues at nanomolar concentrations. Its IC(50) value ranges from 4.1 to 50 nmol/L. The...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-05-2083
更新日期：2006-01-15 00:00:00
abstract：:Mortality or incidence rates of ten major neoplasms in migrants from several countries, their respective countries of origin, their American-born offspring, and United States whites were compared. Rates in succeeding generations of Americans increased most rapidly for colon cancer and most slowly for breast cancer, wi...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1987-11-01 00:00:00
