Purpose: Chemotherapy protocols currently used in children for the treatment of acute lymphoblastic leukemia (ALL) have increased the complete remission rate. However a subset of patients can develop drug resistance or drug side effects, which may hamper the efficacy of treatment and its outcome. An isoform of Manganese-superoxide-dismutase (MnSOD) was recently isolated and sequenced for the first time from a human Liposarcoma cells and obtained in recombinant form. The protein, which is active as an antioxidant enzyme, showed a specific and selective cytotoxicity on many cancer cell lines. The aim of this study was to test the ability of this molecule to inhibit or to interfere with the growth of leukemic cultured pediatric cells. Method: Lymphoblastic cells of children with ALL B or T cell, cultured in RPMI medium, supplemented with 1% PEN STREP and 10% BSA, at 370 C. were treated for 3 hours with rMnSOD. After cell fixation, immunocytochemical reaction at light and electron microscopy was performed by using a specific polyclonal antibody directed against the uncleaved leader peptide of rMnSOD. Western blot assay was used to evaluate the expression of apoptotic proteins (Bcl-2, BAX, Bcl-Xl). Results: Following rMnSOD treatment, ALL cells displayed an intense cytoplasmic positivity to anti-rMnSOD antibody, a reduction in size, nuclear apoptotic fragmentation in some of them and an increased expression of Bcl-2 and BAX genes. Conclusion: rMnSOD is able to enter into cancer ALL cells and induce stimulation of apoptotic pathway These preliminary data are consistent with those previously obtained in breast cancer cells (Mancini et al; Int J Canc,119: 932–943; 2006) and suggest that this molecule may play a role as anti cancer agent in LLA too.
A RECOMBINANT MANGANESE SUPEROXIDE DISMUTASE (rMnSOD) EXERTS A SPECIFIC AND SELECTIVE CYTOTOXIC ACTIVITY ON LEUKEMIC CELLS / F., Casale; V., D’Angelo; Pica, Alessandra; A., Iannotta; A., Mancini; M., Ramaglia; DI SANTI, Annalisa; Basile, Filomena; A., Borrelli; A., Schiattarella; E., Pota; G., Gualdiero; C., Indolfi; G., Pecoraro; P., Indolfi. - STAMPA. - 55:(2010), pp. 852-853. (Intervento presentato al convegno International Society of Paediatric Oncology SIOP XXXXII Congress tenutosi a Boston USA nel October 21-24, 2010) [10.1002/pbc.22779].
A RECOMBINANT MANGANESE SUPEROXIDE DISMUTASE (rMnSOD) EXERTS A SPECIFIC AND SELECTIVE CYTOTOXIC ACTIVITY ON LEUKEMIC CELLS
PICA, ALESSANDRA;DI SANTI, ANNALISA;BASILE, FILOMENA;
2010
Abstract
Purpose: Chemotherapy protocols currently used in children for the treatment of acute lymphoblastic leukemia (ALL) have increased the complete remission rate. However a subset of patients can develop drug resistance or drug side effects, which may hamper the efficacy of treatment and its outcome. An isoform of Manganese-superoxide-dismutase (MnSOD) was recently isolated and sequenced for the first time from a human Liposarcoma cells and obtained in recombinant form. The protein, which is active as an antioxidant enzyme, showed a specific and selective cytotoxicity on many cancer cell lines. The aim of this study was to test the ability of this molecule to inhibit or to interfere with the growth of leukemic cultured pediatric cells. Method: Lymphoblastic cells of children with ALL B or T cell, cultured in RPMI medium, supplemented with 1% PEN STREP and 10% BSA, at 370 C. were treated for 3 hours with rMnSOD. After cell fixation, immunocytochemical reaction at light and electron microscopy was performed by using a specific polyclonal antibody directed against the uncleaved leader peptide of rMnSOD. Western blot assay was used to evaluate the expression of apoptotic proteins (Bcl-2, BAX, Bcl-Xl). Results: Following rMnSOD treatment, ALL cells displayed an intense cytoplasmic positivity to anti-rMnSOD antibody, a reduction in size, nuclear apoptotic fragmentation in some of them and an increased expression of Bcl-2 and BAX genes. Conclusion: rMnSOD is able to enter into cancer ALL cells and induce stimulation of apoptotic pathway These preliminary data are consistent with those previously obtained in breast cancer cells (Mancini et al; Int J Canc,119: 932–943; 2006) and suggest that this molecule may play a role as anti cancer agent in LLA too.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
