Adriamycin activation and oxygen free radical formation in human breast tumor cells: protective role of glutathione peroxidase in adriamycin resistance.

Abstract:

:Previous studies with Adriamycin-sensitive and -resistant (ADRR) MCF-7 human breast tumor cell lines indicated that Adriamycin formed significantly less hydroxyl radical (.OH) as the result of enhanced detoxification of reactive oxygen intermediates in the ADRR cell line. In order to further define the sites of drug activation and the role of detoxification mechanisms in free radical levels, subcellular fractions were isolated from these two cell lines and free radical formation in the presence of Adriamycin was examined by using electron spin resonance spectroscopy. Studies reported here show that considerable NADPH-cytochrome P-450 reductase and NADH dehydrogenase activities were present in microsomes and mitochondria, respectively, and in nuclei obtained from these cells, and the relative activity of NADH dehydrogenase was 2-fold higher in the mitochondrial fraction of ADRR cells compared to the mitochondrial fraction from the parental wild type cells. In the presence of Adriamycin and a reducing cofactor (NADPH or NADH), Adriamycin semiquinone free radical, superoxide anion, and .OH were detected in all these fractions. Although only a small difference in the relative amount of oxy radical formation was detected in tumor microsomes, both mitochondria and nuclei of ADRR cells showed an overall 2-fold decreased formation of oxy radicals. The formation of the free radicals was significantly inhibited by superoxide dismutase, catalase, and dimethyl sulfoxide, indicating that free .OH generation was both superoxide and hydrogen peroxide dependent. The addition of purified glutathione peroxidase likewise inhibited .OH formation in a dose-dependent fashion. Similarly, when the lysate from ADRR cells, which contains 12- to 14-fold more glutathione peroxidase than Adriamycin-sensitive cells, was added to reaction mixtures containing Adriamycin-sensitive cells and Adriamycin, the .OH formation was diminished. Decreased free radical formation in nuclei and mitochondria, as a result of detoxification of hydrogen peroxide by glutathione peroxidase, may be significant in the protection of ADRR cells from Adriamycin-induced cell killing.

journal_name

Cancer Res

journal_title

Cancer research

authors

Sinha BK,Mimnaugh EG,Rajagopalan S,Myers CE

subject

Has Abstract

pub_date

1989-07-15 00:00:00

pages

3844-8

issue

14

eissn

0008-5472

issn

1538-7445

journal_volume

49

pub_type

杂志文章
  • Inhibition of 7,12-dimethylbenz(a)anthracene-induced mammary carcinogenesis by retinyl acetate.

    abstract::The administration of 2.5 mg retinyl acetate daily in the diet to female Sprague-Dawley rats beginning 7 days after the intragastric instillation of either 2.5, 5, or 15 mg 7,12-dimethylbenz(a)anthracene (CMBA) resulted in a reduction in the incidence of benign mammary tumors of 37, 30, and 31%, respectively. An equal...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Moon RC,Grubbs CJ,Sporn MB

    更新日期:1976-07-01 00:00:00

  • Inhibitory effects of antisense cathepsin B cDNA transfection on invasion and motility in a human osteosarcoma cell line.

    abstract::Increased activity, membrane association, and secretion of cathepsin B have been shown to correlate positively with invasiveness and the metastatic properties of many tumor entities. Cathepsin B is able to directly facilitate invasion by degrading extracellular matrix components or to indirectly facilitate invasion by...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Krueger S,Haeckel C,Buehling F,Roessner A

    更新日期:1999-12-01 00:00:00

  • Diet, tobacco use, and fatal prostate cancer: results from the Lutheran Brotherhood Cohort Study.

    abstract::A cohort of 17,633 white males age 35 and older responded to a mailed epidemiological questionnaire in 1966 and was followed until 1986 to determine the risk of cancer associated with diet, tobacco use, and other factors. During the 20-year follow-up, 149 fatal prostate cancer cases were identified. Relative risks for...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Hsing AW,McLaughlin JK,Schuman LM,Bjelke E,Gridley G,Wacholder S,Chien HT,Blot WJ

    更新日期:1990-11-01 00:00:00

  • Specific activation of glucuronide prodrugs by antibody-targeted enzyme conjugates for cancer therapy.

    abstract::Cancer chemotherapy may be improved by increasing antineoplastic drug specificity for tumor cells. We have synthesized a glucuronide prodrug that can be enzymatically converted to an antineoplastic agent at tumor cells that are able to bind beta-glucuronidase-monoclonal antibody conjugates. The glucuronide prodrug BHA...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Wang SM,Chern JW,Yeh MY,Ng JC,Tung E,Roffler SR

    更新日期:1992-08-15 00:00:00

  • p53 mutations in non-small cell lung cancer in Japan: association between mutations and smoking.

    abstract::The p53 gene has been implicated as a tumor suppressor gene involved in the pathogenesis of lung cancer. Our previous study revealed that the p53 gene is frequently mutated with a distinct nucleotide substitution pattern in small cell lung cancer specimens in Japanese patients. In this study, we examined 30 primary, r...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Suzuki H,Takahashi T,Kuroishi T,Suyama M,Ariyoshi Y,Takahashi T,Ueda R

    更新日期:1992-02-01 00:00:00

  • Photosensitization and split-dose recovery in cultured human urinary bladder carcinoma cells containing nonexchangeable hematoporphyrin derivative.

    abstract::The photosensitization and survival recovery of cultured EJ human urinary bladder carcinoma cells containing nonexchangeable hematoporphyrin derivative (HPD) were studied. Cultures were incubated at 37 degrees C in growth medium supplemented with HPD (50 micrograms/ml) and 5% fetal bovine serum for 12 h followed by in...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Bellnier DA,Lin CW

    更新日期:1985-06-01 00:00:00

  • Wortmannin, a potent and selective inhibitor of phosphatidylinositol-3-kinase.

    abstract::Phosphatidylinositol-3-kinase is an important enzyme for intracellular signaling. The microbial product wortmannin and some of its analogues have been shown to be potent inhibitors of phosphatidylinositol-3-kinase. The 50% inhibitory concentration for inhibition by wortmannin is 2 to 4 nM. Kinetic analysis demonstrate...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Powis G,Bonjouklian R,Berggren MM,Gallegos A,Abraham R,Ashendel C,Zalkow L,Matter WF,Dodge J,Grindey G

    更新日期:1994-05-01 00:00:00

  • Loss of heterozygosity patterns provide fingerprints for genetic heterogeneity in multistep cancer progression of tobacco smoke-induced non-small cell lung cancer.

    abstract::Dilution end point loss of heterozygosity (LOH) analysis, a novel approach for the analysis of LOH, was used to evaluate allelic losses with the use of 21 highly polymorphic microsatellite markers at nine chromosomal sites most frequently affected in smoking-related non-small cell lung cancers. Allelotyping was done f...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-04-3297

    authors: Pan H,Califano J,Ponte JF,Russo AL,Cheng KH,Thiagalingam A,Nemani P,Sidransky D,Thiagalingam S

    更新日期:2005-03-01 00:00:00

  • Potentiation of the antitumor activity of 5-fluorouracil in colon carcinoma cells by the combination of interferon and deoxyribonucleosides results from complementary effects on thymidine phosphorylase.

    abstract::alpha-Interferon (IFN alpha) potentiates the cytotoxicity of 5-fluorouracil (FUra) in vitro, and the combination has clinical efficacy in advanced colorectal cancer. We have reported previously an IFN alpha-mediated elevation in cellular FdUMP levels accompanied by the stimulation of thymidine phosphorylase (TP) activ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Schwartz EL,Baptiste N,O'Connor CJ,Wadler S,Otter BA

    更新日期:1994-03-15 00:00:00

  • CD44 potentiates the adherence of metastatic prostate and breast cancer cells to bone marrow endothelial cells.

    abstract::The aim of this current study was to examine the significance of CD44 expression in mediating cancer cell adhesion to human bone marrow endothelial cell(s) (hBMEC). Differential CD44 expression on two metastatic prostate cancer cell lines, PC3 (CD44 +ve) and DU145 (CD44 -ve) and four breast cancer cell lines was confi...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-04-0389

    authors: Draffin JE,McFarlane S,Hill A,Johnston PG,Waugh DJ

    更新日期:2004-08-15 00:00:00

  • DINC 2.0: A New Protein-Peptide Docking Webserver Using an Incremental Approach.

    abstract::Molecular docking is a standard computational approach to predict binding modes of protein-ligand complexes by exploring alternative orientations and conformations of the ligand (i.e., by exploring ligand flexibility). Docking tools are largely used for virtual screening of small drug-like molecules, but their accurac...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-17-0511

    authors: Antunes DA,Moll M,Devaurs D,Jackson KR,Lizée G,Kavraki LE

    更新日期:2017-11-01 00:00:00

  • EMP3, a myelin-related gene located in the critical 19q13.3 region, is epigenetically silenced and exhibits features of a candidate tumor suppressor in glioma and neuroblastoma.

    abstract::The presence of common genomic deletions in the 19q13 chromosomal region in neuroblastomas and gliomas strongly suggests the presence of a putative tumor suppressor gene for these neoplasms in this region that, despite much effort, has not yet been identified. In an attempt to address this issue, we compared the expre...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-04-4283

    authors: Alaminos M,Dávalos V,Ropero S,Setién F,Paz MF,Herranz M,Fraga MF,Mora J,Cheung NK,Gerald WL,Esteller M

    更新日期:2005-04-01 00:00:00

  • Radiation-induced apoptosis in a murine T-cell hybridoma.

    abstract::Induction of an apoptotic cell death was studied in a mouse T-cell hybridoma. Apoptosis was induced in these cells following exposure to dexamethasone, X-radiation, 43 degrees C heat shock, A254 light, and hydrogen peroxide. In 5-Gy-exposed cells, a radiation-induced G2 phase cell cycle progression block was maximum b...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Warters RL

    更新日期:1992-02-15 00:00:00

  • Antagonistic effect of aclarubicin on the cytotoxicity of etoposide and 4'-(9-acridinylamino)methanesulfon-m-anisidide in human small cell lung cancer cell lines and on topoisomerase II-mediated DNA cleavage.

    abstract::The effect of combinations of the anthracycline aclarubicin and the topoisomerase II targeting drugs 4'-demethylepipodophyllotoxin-9-(4,6-O-ethylidene-beta-D-glucopyra noside) (VP-16) and 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA) was investigated in a clonogenic assay. The cytotoxicity of VP-16 was almos...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Jensen PB,Sørensen BS,Demant EJ,Sehested M,Jensen PS,Vindeløv L,Hansen HH

    更新日期:1990-06-01 00:00:00

  • Chromatin Remodeling Factor LSH Drives Cancer Progression by Suppressing the Activity of Fumarate Hydratase.

    abstract::Chromatin modification is pivotal to the epithelial-mesenchymal transition (EMT), which confers potent metastatic potential to cancer cells. Here, we report a role for the chromatin remodeling factor lymphoid-specific helicase (LSH) in nasopharyngeal carcinoma (NPC), a prevalent cancer in China. LSH expression was inc...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-16-0268

    authors: He X,Yan B,Liu S,Jia J,Lai W,Xin X,Tang CE,Luo D,Tan T,Jiang Y,Shi Y,Liu Y,Xiao D,Chen L,Liu S,Mao C,Yin G,Cheng Y,Fan J,Cao Y,Muegge K,Tao Y

    更新日期:2016-10-01 00:00:00

  • Tumor Cell Invasion-Not All Barriers Are Created Equal.

    abstract::The importance of invasion in the complex process of metastasis, although now well established, has been studied with increasing molecular detail due to the development of robust in vitro experimental assays. In this issue of Cancer Research, we highlight a paper published by George Poste and colleagues that compared ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-16-0550

    authors: Welch DR

    更新日期:2016-04-01 00:00:00

  • Successful chemotherapy of experimental neuroendocrine lung tumors in hamsters with an antagonist of Ca2+/calmodulin.

    abstract::The chemotherapeutic effect of B859-35, the (-)-enantiomer of dihydropyrine 3-methyl-5-3-(4,4-diphenyl-1-piperidinyl)-propyl-1,4-dihydro-2,6-dimethy l-4- (3-nitrophenyl)-pyridine-3,5-dicarboxylate-hydrochloride (niguldipine), was tested on tumors induced in Syrian golden hamsters by N-nitrosodiethylamine (DEN). Periph...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Schuller HM,Correa E,Orloff M,Reznik GK

    更新日期:1990-03-01 00:00:00

  • In vitro and in vivo cytotoxicity of rhodamine 123 combined with hyperthermia.

    abstract::Because both Rhodamine 123 (R123) and hyperthermia have been shown to be cytotoxic, we examined their effect, independently and in combination, on five different human malignant cell lines in vitro and on cultured melanoma cells grown intradermally in nude mice. The cell lines examined include two human melanomas, UCL...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Goffney WH,Wong JH,Kern DH,Chase D,Krag DN,Storm FK

    更新日期:1990-02-01 00:00:00

  • Effects of bleomycin on human tongue carcinoma cells as revealed by electron microscopy.

    abstract::Five patients with tongue carcinoma were treated for 20 days with bleomycin, 15 mg/day, given by one-shot infusion through the superficial temporal artery. Specimens were taken 7, 14, and 20 days after the initial administration for light and electron microscope observations. The first alterations observed were the de...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Yasuzumi G,Hyo Y,Hoshiya T,Yasuzumi F

    更新日期:1976-10-01 00:00:00

  • Live-cell imaging of invasion and intravasation in an artificial microvessel platform.

    abstract::Methods to visualize metastasis exist, but additional tools to better define the biologic and physical processes underlying invasion and intravasation are still needed. One difficulty in studying metastasis stems from the complexity of the interface between the tumor microenvironment and the vascular system. Here, we ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-14-1042

    authors: Wong AD,Searson PC

    更新日期:2014-09-01 00:00:00

  • Focused ultrasound delivers targeted immune cells to metastatic brain tumors.

    abstract::Natural killer (NK) cells are cytotoxic lymphocytes involved in innate immunity. NK-92, a human NK cell line, may be targeted to tumor-associated antigens in solid malignancies where it exhibits antitumor efficacy, but its clinical utility for treating brain tumors is limited by an inability to cross the blood-brain b...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-12-2609

    authors: Alkins R,Burgess A,Ganguly M,Francia G,Kerbel R,Wels WS,Hynynen K

    更新日期:2013-03-15 00:00:00

  • IgG2a induced by interleukin (IL) 12-producing tumor cell vaccines but not IgG1 induced by IL-4 vaccine is associated with the eradication of experimental metastases.

    abstract::We evaluated whether antibody response correlates with tumor therapy by cytokine gene-modified tumor cell vaccines. To characterize the antibody (Ab) response against a known antigen, colon carcinoma C26 cells and C26 variants engineered to produce interleukin (IL) 12 or IL-4 were further transduced to express the hum...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Rodolfo M,Melani C,Zilocchi C,Cappetti B,Luison E,Arioli I,Parenza M,Canevari S,Colombo MP

    更新日期:1998-12-15 00:00:00

  • Expression of activation-induced cytidine deaminase is confined to B-cell non-Hodgkin's lymphomas of germinal-center phenotype.

    abstract::Activation-induced cytidine deaminase (AID) is essential for somatic hypermutation and class switch recombination of the immunoglobulin (IG) genes in B cells. It has recently been proposed that AID, as the newly identified DNA mutator in man, may be instrumental in initiation and progression of B-cell non-Hodgkin's ly...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Smit LA,Bende RJ,Aten J,Guikema JE,Aarts WM,van Noesel CJ

    更新日期:2003-07-15 00:00:00

  • Classification and risk assessment of individuals with familial polyposis, Gardner's syndrome, and familial non-polyposis colon cancer from [3H]thymidine labeling patterns in colonic epithelial cells.

    abstract::A probabilistic analysis has been developed to assist the binary classification and risk assessment of members of familial colon cancer kindreds. The analysis is based on the microautoradiographic observation of [3H]thymidine-labeled epithelial cells in colonic mucosa of the kindred members. From biopsies of colonic m...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Lipkin M,Blattner WA,Gardner EJ,Burt RW,Lynch H,Deschner E,Winawer S,Fraumeni JF Jr

    更新日期:1984-09-01 00:00:00

  • Suppression of tumorigenicity of human prostate cancer cells by introduction of human chromosome del(12)(q13).

    abstract::The introduction of normal chromosomes into tumor cells by microcell fusion-mediated transfer is a powerful technique to identify putative tumor suppressor genes. We have used this approach to independently transfer human chromosomes 3 and 12 into a human prostate cancer cell line, DU 145. We showed that while the ext...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Bérubé NG,Speevak MD,Chevrette M

    更新日期:1994-06-15 00:00:00

  • Distinct structural domains within C19ORF5 support association with stabilized microtubules and mitochondrial aggregation and genome destruction.

    abstract::C19ORF5 is a sequence homologue of microtubule-associated proteins MAP1A/MAP1B of unknown function, except for its association with mitochondria-associated proteins and the paclitaxel-like microtubule stabilizer and candidate tumor suppressor RASSF1A. Here, we show that when overexpressed in mammalian cells the recomb...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-04-3865

    authors: Liu L,Vo A,Liu G,McKeehan WL

    更新日期:2005-05-15 00:00:00

  • CHK1 Inhibition Is Synthetically Lethal with Loss of B-Family DNA Polymerase Function in Human Lung and Colorectal Cancer Cells.

    abstract::Checkpoint kinase 1 (CHK1) is a key mediator of the DNA damage response that regulates cell-cycle progression, DNA damage repair, and DNA replication. Small-molecule CHK1 inhibitors sensitize cancer cells to genotoxic agents and have shown single-agent preclinical activity in cancers with high levels of replication st...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-19-1372

    authors: Rogers RF,Walton MI,Cherry DL,Collins I,Clarke PA,Garrett MD,Workman P

    更新日期:2020-04-15 00:00:00

  • Cell-mediated antitumor immunity in breast cancer patients evaluated by antigen-induced leukocyte adherence inhibition in test tubes.

    abstract::Tumor antigen-induced inhibition of leukocyte adherence was adapted and modified for use in glass test tubes for the study of cell-mediated antitumor immunity to human adenocarcinoma of the breast. Peripheral blood leukocytes from 40 to 47 patients with proven breast cancer responded to an antigenic extract of breast ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Grosser N,Thomson DM

    更新日期:1975-09-01 00:00:00

  • Identification of a tumor-suppressive human-specific microRNA within the FHIT tumor-suppressor gene.

    abstract::Loss or attenuated expression of the tumor-suppressor gene FHIT is associated paradoxically with poor progression of human tumors. Fhit promotes apoptosis and regulates reactive oxygen species; however, the mechanism by which Fhit inhibits tumor growth in animals remains unclear. In this study, we used a multidiscipli...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-13-3279

    authors: Hu B,Ying X,Wang J,Piriyapongsa J,Jordan IK,Sheng J,Yu F,Zhao P,Li Y,Wang H,Ng WL,Hu S,Wang X,Wang C,Zheng X,Li W,Curran WJ,Wang Y

    更新日期:2014-04-15 00:00:00

  • Immunization against feline oncarnavirus disease using a killed tumor cell vaccine.

    abstract::Specific pathogen-free cats were immunized with an inactivated feline oncornavirus tumor cell vaccine. Immunized cats produced high antibody titers to the feline oncornavirus-associated cell membrane antigen and were protected from oncogenic feline sarcoma virus challenge. However, immunization did not produce virus-n...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Olsen RG,Hoover EA,Mathes LE,Heding L,Schaller JP

    更新日期:1976-10-01 00:00:00