Overcoming drug-resistant cancer by a newly developed copper chelate through host-protective cytokine-mediated apoptosis

Publication type:
Journal article
Metadata:
Autoren
  • Ananda Mookerjee
  • Jayati Mookerjee Basu
  • Pranabanancla Dutta
  • Surajit Majumder
  • Sankar Bhattacharyya
  • Jaydip Biswas
  • Smarajit Pal
  • Pratima Mukherjee
  • Sanghamitra Raha
  • Rathindra N Baral
  • Tania Das
  • Thomas Efferth
  • Gourinkar Sa sa
  • Shyamal Roy
  • Soumitra K Choudhuri
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000239373200029&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1158/1078-0432.CCR-06-0001
eISSN
1557-3265
Externe Identifier
  • Clarivate Analytics Document Solution ID: 068KR
  • PubMed Identifier: 16857809
ISSN
1078-0432
Ausgabe der Veröffentlichung
14
Zeitschrift
CLINICAL CANCER RESEARCH
Paginierung
4339 - 4349
Datum der Veröffentlichung
2006
Status
Published
Titel
Overcoming drug-resistant cancer by a newly developed copper chelate through host-protective cytokine-mediated apoptosis
Sub types
  • Article
Ausgabe der Zeitschrift
12

Data source: Web of Science (Lite)

Other metadata sources:
Abstract
<jats:title>Abstract</jats:title><jats:p>Purpose: Previously, we have synthesized and characterized a novel Cu(II) complex, copper N-(2-hydroxy acetophenone) glycinate (CuNG). Herein, we have determined the efficacy of CuNG in overcoming multidrug-resistant cancer using drug-resistant murine and human cancer cell lines.</jats:p><jats:p>Experimental Design: Action of CuNG following single i.m. administration (5 mg/kg body weight) was tested in vivo on doxorubicin-resistant Ehrlich ascites carcinoma (EAC/Dox)–bearing mice and doxorubicin-resistant sarcoma 180–bearing mice. Tumor size, ascitic load, and survival rates were monitored at regular intervals. Apoptosis of cancer cells was determined by cell cycle analysis, confocal microscopy, Annexin V binding, and terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling assay ex vivo. IFN-γ and tumor necrosis factor-α were assayed in the culture supernatants of in vivo and in vitro CuNG-treated splenic mononuclear cells from EAC/Dox-bearing mice and their apoptogenic effect was determined. Source of IFN-γ and changes in number of T regulatory marker-bearing cells in the tumor site following CuNG treatment were investigated by flow cytometry. Supernatants of in vitro CuNG-treated cultures of peripheral blood mononuclear cells from different drug-insensitive cancer patients were tested for presence of the apoptogenic cytokine IFN-γ and its involvement in induction of apoptosis of doxorubicin-resistant CEM/ADR5000 cells.</jats:p><jats:p>Results: CuNG treatment could resolve drug-resistant cancers through induction of apoptogenic cytokines, such as IFN-γ and/or tumor necrosis factor-α, from splenic mononuclear cells or patient peripheral blood mononuclear cells and reduce the number of T regulatory marker-bearing cells while increase infiltration of IFN-γ-producing T cells in the ascetic tumor site.</jats:p><jats:p>Conclusion: Our results show the potential usefulness of CuNG in immunotherapy of drug-resistant cancers irrespective of multidrug resistance phenotype.</jats:p>
Autoren
  • Ananda Mookerjee
  • Jayati Mookerjee Basu
  • Pranabananda Dutta
  • Surajit Majumder
  • Sankar Bhattacharyya
  • Jaydip Biswas
  • Smarajit Pal
  • Pratima Mukherjee
  • Sanghamitra Raha
  • Rathindra N Baral
  • Tania Das
  • Thomas Efferth
  • Gourisankar Sa
  • Shyamal Roy
  • Soumitra K Choudhuri
DOI
10.1158/1078-0432.ccr-06-0001
eISSN
1557-3265
ISSN
1078-0432
Ausgabe der Veröffentlichung
14
Zeitschrift
Clinical Cancer Research
Sprache
en
Online publication date
2006
Paginierung
4339 - 4349
Datum der Veröffentlichung
2006
Status
Published
Herausgeber
American Association for Cancer Research (AACR)
Herausgeber URL
http://dx.doi.org/10.1158/1078-0432.ccr-06-0001
Datum der Datenerfassung
2023
Titel
Overcoming Drug-Resistant Cancer by a Newly Developed Copper Chelate through Host-Protective Cytokine-Mediated Apoptosis
Ausgabe der Zeitschrift
12

Data source: Crossref

Abstract
<h4>Purpose</h4>Previously, we have synthesized and characterized a novel Cu(II) complex, copper N-(2-hydroxy acetophenone) glycinate (CuNG). Herein, we have determined the efficacy of CuNG in overcoming multidrug-resistant cancer using drug-resistant murine and human cancer cell lines.<h4>Experimental design</h4>Action of CuNG following single i.m. administration (5 mg/kg body weight) was tested in vivo on doxorubicin-resistant Ehrlich ascites carcinoma (EAC/Dox)-bearing mice and doxorubicin-resistant sarcoma 180-bearing mice. Tumor size, ascitic load, and survival rates were monitored at regular intervals. Apoptosis of cancer cells was determined by cell cycle analysis, confocal microscopy, Annexin V binding, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay ex vivo. IFN-gamma and tumor necrosis factor-alpha were assayed in the culture supernatants of in vivo and in vitro CuNG-treated splenic mononuclear cells from EAC/Dox-bearing mice and their apoptogenic effect was determined. Source of IFN-gamma and changes in number of T regulatory marker-bearing cells in the tumor site following CuNG treatment were investigated by flow cytometry. Supernatants of in vitro CuNG-treated cultures of peripheral blood mononuclear cells from different drug-insensitive cancer patients were tested for presence of the apoptogenic cytokine IFN-gamma and its involvement in induction of apoptosis of doxorubicin-resistant CEM/ADR5000 cells.<h4>Results</h4>CuNG treatment could resolve drug-resistant cancers through induction of apoptogenic cytokines, such as IFN-gamma and/or tumor necrosis factor-alpha, from splenic mononuclear cells or patient peripheral blood mononuclear cells and reduce the number of T regulatory marker-bearing cells while increase infiltration of IFN-gamma-producing T cells in the ascetic tumor site.<h4>Conclusion</h4>Our results show the potential usefulness of CuNG in immunotherapy of drug-resistant cancers irrespective of multidrug resistance phenotype.
Addresses
  • Department of Environmental Carcinogenesis and Toxicology, Chittaranjan National Cancer Institute, India.
Autoren
  • Ananda Mookerjee
  • Jayati Mookerjee Basu
  • Pranabananda Dutta
  • Surajit Majumder
  • Sankar Bhattacharyya
  • Jaydip Biswas
  • Smarajit Pal
  • Pratima Mukherjee
  • Sanghamitra Raha
  • Rathindra N Baral
  • Tania Das
  • Thomas Efferth
  • Thomas Efferth
  • Gourisankar Sa
  • Shyamal Roy
  • Soumitra K Choudhuri
DOI
10.1158/1078-0432.ccr-06-0001
eISSN
1557-3265
Externe Identifier
  • PubMed Identifier: 16857809
Open access
false
ISSN
1078-0432
Ausgabe der Veröffentlichung
14 Pt 1
Zeitschrift
Clinical cancer research : an official journal of the American Association for Cancer Research
Schlüsselwörter
  • Lymph Nodes
  • Spleen
  • Leukocytes, Mononuclear
  • Cell Line, Tumor
  • Animals
  • Humans
  • Mice
  • Neoplasms
  • Carcinoma, Ehrlich Tumor
  • Copper
  • Doxorubicin
  • Antineoplastic Agents
  • Cytokines
  • Chelating Agents
  • Neoplasm Transplantation
  • Drug Resistance, Multiple
  • Apoptosis
  • Cell Proliferation
  • Drug Resistance, Neoplasm
Sprache
eng
Medium
Print
Paginierung
4339 - 4349
Datum der Veröffentlichung
2006
Status
Published
Datum der Datenerfassung
2006
Titel
Overcoming drug-resistant cancer by a newly developed copper chelate through host-protective cytokine-mediated apoptosis.
Sub types
  • Research Support, Non-U.S. Gov't
  • Journal Article
Ausgabe der Zeitschrift
12

Data source: Europe PubMed Central

Abstract
PURPOSE: Previously, we have synthesized and characterized a novel Cu(II) complex, copper N-(2-hydroxy acetophenone) glycinate (CuNG). Herein, we have determined the efficacy of CuNG in overcoming multidrug-resistant cancer using drug-resistant murine and human cancer cell lines. EXPERIMENTAL DESIGN: Action of CuNG following single i.m. administration (5 mg/kg body weight) was tested in vivo on doxorubicin-resistant Ehrlich ascites carcinoma (EAC/Dox)-bearing mice and doxorubicin-resistant sarcoma 180-bearing mice. Tumor size, ascitic load, and survival rates were monitored at regular intervals. Apoptosis of cancer cells was determined by cell cycle analysis, confocal microscopy, Annexin V binding, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay ex vivo. IFN-gamma and tumor necrosis factor-alpha were assayed in the culture supernatants of in vivo and in vitro CuNG-treated splenic mononuclear cells from EAC/Dox-bearing mice and their apoptogenic effect was determined. Source of IFN-gamma and changes in number of T regulatory marker-bearing cells in the tumor site following CuNG treatment were investigated by flow cytometry. Supernatants of in vitro CuNG-treated cultures of peripheral blood mononuclear cells from different drug-insensitive cancer patients were tested for presence of the apoptogenic cytokine IFN-gamma and its involvement in induction of apoptosis of doxorubicin-resistant CEM/ADR5000 cells. RESULTS: CuNG treatment could resolve drug-resistant cancers through induction of apoptogenic cytokines, such as IFN-gamma and/or tumor necrosis factor-alpha, from splenic mononuclear cells or patient peripheral blood mononuclear cells and reduce the number of T regulatory marker-bearing cells while increase infiltration of IFN-gamma-producing T cells in the ascetic tumor site. CONCLUSION: Our results show the potential usefulness of CuNG in immunotherapy of drug-resistant cancers irrespective of multidrug resistance phenotype.
Autoren
  • Ananda Mookerjee
  • Jayati Mookerjee Basu
  • Pranabananda Dutta
  • Surajit Majumder
  • Sankar Bhattacharyya
  • Jaydip Biswas
  • Smarajit Pal
  • Pratima Mukherjee
  • Sanghamitra Raha
  • Rathindra N Baral
  • Tania Das
  • Thomas Efferth
  • Gourisankar Sa
  • Shyamal Roy
  • Soumitra K Choudhuri
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/16857809
DOI
10.1158/1078-0432.CCR-06-0001
ISSN
1078-0432
Ausgabe der Veröffentlichung
14 Pt 1
Zeitschrift
Clin Cancer Res
Schlüsselwörter
  • Animals
  • Antineoplastic Agents
  • Apoptosis
  • Carcinoma, Ehrlich Tumor
  • Cell Line, Tumor
  • Cell Proliferation
  • Chelating Agents
  • Copper
  • Cytokines
  • Doxorubicin
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Humans
  • Leukocytes, Mononuclear
  • Lymph Nodes
  • Mice
  • Neoplasm Transplantation
  • Neoplasms
  • Spleen
Sprache
eng
Country
United States
Paginierung
4339 - 4349
PII
12/14/4339
Datum der Veröffentlichung
2006
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2007
Titel
Overcoming drug-resistant cancer by a newly developed copper chelate through host-protective cytokine-mediated apoptosis.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
12

Data source: PubMed

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