title: An in vitro and in vivo study of a novel zinc complex, zinc N-(2-hydroxyacetophenone)glycinate to overcome multidrug resistance in cancer.
abstract: 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.
authors.affiliation: Department of In Vitro Carcinogenesis and Cellular Chemotherapy, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, 700 026, Kolkata, India.
authors.forename: Ruma Dey
authors.initials: RD
authors.lastname: Ghosh
authors.forename: Satyajit
authors.initials: S
authors.lastname: Das
authors.forename: Avishek
authors.initials: A
authors.lastname: Ganguly
authors.forename: Kaushik
authors.initials: K
authors.lastname: Banerjee
authors.forename: Paramita
authors.initials: P
authors.lastname: Chakraborty
authors.forename: Avijit
authors.initials: A
authors.lastname: Sarkar
authors.forename: Mitali
authors.initials: M
authors.lastname: Chatterjee
authors.forename: Ashis
authors.initials: A
authors.lastname: Nanda
authors.forename: Kiran
authors.initials: K
authors.lastname: Pradhan
authors.forename: Soumitra K
authors.initials: SK
authors.lastname: Choudhuri
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002286:Carcinoma, Ehrlich Tumor; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D051379:Mice; D017382:Reactive Oxygen Species / Q000378:metabolism; D014747:Vinblastine / Q000494:pharmacology; D015032:Zinc / Q000737:chemistry
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D056831:Coordination Complexes; D017382:Reactive Oxygen Species; D014747:Vinblastine; D004317:Doxorubicin; D015032:Zinc