An in vitro and in vivo study of a novel zinc complex, zinc N-(2-hydroxyacetophenone)glycinate to overcome multidrug resistance in cancer

Multiple drug resistance (MDR) remains a major clinical challenge for cancer treatment. P-glycoprotein is the major contributor and they exceed their role in the chemotherapy resistance of most of the malignancies. Attempts in several preclinical and clinical studies to reverse the MDR phenomenon by...

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Published in:Dalton transactions : an international journal of inorganic chemistry 2011-11, Vol.40 (41), p.10873
Main Authors: Ghosh, Ruma Dey, Das, Satyajit, Ganguly, Avishek, Banerjee, Kaushik, Chakraborty, Paramita, Sarkar, Avijit, Chatterjee, Mitali, Nanda, Ashis, Pradhan, Kiran, Choudhuri, Soumitra K
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Apoptosis - drug effects
ATP-Binding Cassette, Sub-Family B, Member 1 - genetics
ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism
Carcinoma, Ehrlich Tumor
Cell Line, Tumor
Coordination Complexes - chemical synthesis
Coordination Complexes - chemistry
Coordination Complexes - pharmacology
Doxorubicin - pharmacology
Drug Resistance, Neoplasm - drug effects
Female
Humans
Mice
Reactive Oxygen Species - metabolism
Vinblastine - pharmacology
Zinc - chemistry
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Summary:Multiple drug resistance (MDR) remains a major clinical challenge for cancer treatment. P-glycoprotein is the major contributor and they exceed their role in the chemotherapy resistance of most of the malignancies. Attempts in several preclinical and clinical studies to reverse the MDR phenomenon by using MDR modulators have not yet generated promising results. In the present study, a co-ordination complex of zinc viz., Zn N-(2-hydroxyacetophenone)glycinate (ZnNG) has been synthesized, characterized and its antitumour activity was tested in vitro against drug sensitive and resistant human T-lymphoblastic leukemic cell lines (CCRF/CEM and CEM/ADR5000 respectively) and in vivo against Ehrlich ascites carcinoma (EAC) implanted in female Swiss albino mice. To evaluate the cytotoxic potential of ZnNG, we used sensitive CCRF/CEM and drug resistant CEM/ADR 5000 cell lines in vitro. Moreover, ZnNG also has the potential ability to reverse the multidrug resistance phenotype in drug resistant CEM/ADR 5000 cell line and induces apoptosis in combination with vinblastine. ZnNG remarkably increases the life span of Swiss albino mice bearing sensitive and doxorubicin resistant subline of EAC in presence and in absence of doxorubicin. In addition, intraperitoneal application of ZnNG in mice does not show any systemic toxicity in preliminary trials in normal mice. To conclude, a novel metal chelate of zinc viz., ZnNG, may be a promising therapeutic agent against sensitive as well as drug resistant cancers.
ISSN:1477-9226
1477-9234
DOI:10.1039/c1dt10501a