Overcoming Drug-Resistant Cancer by a Newly Developed Copper Chelate throughHost-Protective Cytokine-MediatedApoptosis
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Overcoming Drug-Resistant Cancer by a Newly Developed Copper
Chelate throughHost-Protective Cytokine-MediatedApoptosis
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| Creator |
Mookerjee, Ananda
Mookerjee Basu, Jayati Dutta, Pranabananda Majumder, Surajit Bhattacharyya, Sankar Biswas, Jaydip Pal, Smarajit Mukherjee, Pratima Raha, Sanghamitra Baral, Rathindra N Das, Tania Efferth, Thomas Sa, Gouri Shankar Ray, Shyamal Choudhuri, Soumitra K |
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| Subject |
Cancer Biology and Inflammatory Disorder Division
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| Description |
Previously, we have synthesized and characterized a novel Cu(II) complex, copper N-(2-hydroxy acetophenone) glycinate (CuNG).Herein,wehave determined the efficacyofCuNG
in overcomingmultidrug-resistant cancer using drug-resistantmurine 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 cellcy cle analysis, confocal microscopy, Annexin V binding, and terminald eoxynucleotidyl
transferase ^mediated dUTP nick end labeling assay ex vivo. IFN-g and tumor necrosis factor-a
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-g and changes in number of Tregulatory 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-g and its involvement in induction of
apoptosis of doxorubicin-resistant CEM/ADR5000 cells.
Results: CuNGtreatment could resolve drug-resistant cancers through induction of apoptogenic
cytokines, such as IFN-g and/or tumor necrosis factor-a, from splenic mononuclear cells or
patient peripheral bloodmononuclear cells and reduce the number ofTregulatory marker-bearing
cells while increase infiltration of IFN-g-producingTcells in the ascetic tumor site.
Conclusion: Our results show the potential usefulness of CuNG in immunotherapy of drugresistant
cancers irrespective of multidrug resistance phenotype.
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| Date |
2006
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/436/1/CLINICAL_CANCER_RESEARCH%2C_12(_14)%2C_4339%2D4349_[61].pdf
Mookerjee, Ananda and Mookerjee Basu, Jayati and Dutta, Pranabananda and Majumder, Surajit and Bhattacharyya, Sankar and Biswas, Jaydip and Pal, Smarajit and Mukherjee, Pratima and Raha, Sanghamitra and Baral, Rathindra N and Das, Tania and Efferth, Thomas and Sa, Gouri Shankar and Ray, Shyamal and Choudhuri, Soumitra K (2006) Overcoming Drug-Resistant Cancer by a Newly Developed Copper Chelate throughHost-Protective Cytokine-MediatedApoptosis. Clin Cancer Res, 12 (14). pp. 4339-4349. |
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| Relation |
htpp://dx.doi.org/10.1158/1078-0432.CCR-06-0001
http://www.eprints.iicb.res.in/436/ |
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