Overcoming drug-resistant cancer by a newly developed copper chelate through host-protective cytokine-mediated apoptosis
Metadata of CSIR Papers
View Archive Info| Field | Value | |
| Title |
Overcoming drug-resistant cancer by a newly developed copper chelate through host-protective cytokine-mediated apoptosis
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| Creator |
Mookerjee, A
Basu, JM Dutta, P Majumder, S Bhattacharyya, S Biswas, J Pal, S Mukherjee, P Raha, S Baral, RN Das, T Efferth, T Sa, G Roy, S Choudhuri, SK |
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| Subject |
Oncology
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| Description |
Purpose: Previously, we have synthesized and characterized a novel Cu(II) complex, copper N-(2-hydroxyacetophenone) 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 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.
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| Publisher |
AMER ASSOC CANCER RESEARCHPHILADELPHIA615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
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| Date |
2011-09-20T12:12:11Z
2011-09-20T12:12:11Z 2006 |
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| Type |
Article
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| Identifier |
CLINICAL CANCER RESEARCH
1078-0432 http://hdl.handle.net/123456789/14158 |
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| Language |
English
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