title: A novel manganese complex, Mn-(II) N-(2-hydroxy acetophenone) glycinate overcomes multidrug-resistance in cancer.
abstract: Multidrug resistance (MDR) remains a significant problem for effective cancer chemotherapy. In spite of considerable advances in drug discovery, most of the cancer cases still stay incurable because of resistance to chemotherapy. We synthesized a novel, Mn (II) complex (chelate), viz., manganese N-(2-hydroxy acetophenone) glycinate (MnNG) that exhibits considerable efficacy to overcome drug resistant cancer. The antiproliferative activity of MnNG was studied on doxorubicin resistant and sensitive human T lymphoblastic leukemia cells (CEM/ADR 5000 and CCRF/CEM). MnNG induced apoptosis significantly in CEM/ADR 5000 cells probably through generation of reactive oxygen species. Moreover, intraperitoneal (i.p.) application of MnNG at non-toxic doses caused significant increase in the life-span of Swiss albino mice bearing sensitive and doxorubicin resistant subline of Ehrlich ascites carcinoma cells.
authors.affiliation: Department of In Vitro Carcinogenesis and Cellular Chemotherapy, Chittaranjan National Cancer Institute, Kolkata, India.
authors.forename: Ruma Dey
authors.initials: RD
authors.lastname: Ghosh
authors.forename: Kaushik
authors.initials: K
authors.lastname: Banerjee
authors.forename: Satyajit
authors.initials: S
authors.lastname: Das
authors.forename: Avishek
authors.initials: A
authors.lastname: Ganguly
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: Soumitra K
authors.initials: SK
authors.lastname: Choudhuri
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004317:Doxorubicin; D018432:Drug Resistance, Multiple; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D008345:Manganese / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy*; D009942:Organometallic Compounds / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D008345:Manganese; D004317:Doxorubicin; D005998:Glycine
keywords: 2′,7′-dihydrodichlorofluorescin diacetate; 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide; 5,5′- Dithio bis(2-nitrobenzoic acid); ALP; Apoptosis; DTNB; EAC; Ehrlich ascites carcinoma; FITC; GSH; H(2)-DCFDA; IC(50); LD(50); Leukemic cells; MDR; MTT; Manganese complex; MnNG; Multidrug resistance; P-glycoprotein; P-gp; PHAG; PI; ROS; RT-PCR; SGOT; SGPT; alkaline phosphatase; dose for 50% death of animals; dose for 50% growth inhibition of cell; fluoroscein isothiocyanate conjugate; glutathione; manganese N-(2-hydroxy acetophenone) glycinate; multidrug resistance; potassium N-(2-hydroxy acetophenone) glycinate; propidium iodide; reactive oxygen species; reverse transcription-polymerase chain reaction; serum glutamate ortho-transferase; serum glutamine pyruvate transaminase