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3 results on '"Laura Alaniz"'

1. Hyaluronan induces migration of multidrug-resistant lymphoma cell lines in vitro through Tiam1 activation by a PI3K-dependent mechanism

Author

Rosalía I. Cordo-Russo, Silvia E. Hajos, Silvina Lompardía, Laura Alaniz, Elida Alvarez, Mariana Garcia, Guillermo A. Blanco, and Natalia Saccodossi

Subjects
Cancer Research, Lymphoma, Biology, Ciencias Biológicas, Mice, Phosphatidylinositol 3-Kinases, Cell Movement, Cell Line, Tumor, medicine, Tiam1, Animals, Guanine Nucleotide Exchange Factors, T-Lymphoma Invasion and Metastasis-inducing Protein 1, Hyaluronic Acid, Cytoskeleton, Hyaluronan, Migration, PI3K/AKT/mTOR pathway, Cell migration, Hematology, Bioquímica y Biología Molecular, medicine.disease, Drug Resistance, Multiple, In vitro, Cell biology, Multiple drug resistance, Oncology, Cell culture, Signal transduction, Multidrug Resistance, CIENCIAS NATURALES Y EXACTAS, Signal Transduction
Abstract

Hyaluronan (HA) modulates multidrug resistance (MDR) as well as cell migration. Tiam1 is involved in cytoskeleton reorganization during tumor invasion. In this report we show the relationship among HA, Tiam1, migration and MDR in murine lymphoma cell lines. We observed that MDR cells presented higher migratory capacity towards HA in vitro as well as higher constitutive active Tiam1 expression than the sensitive cell line. Besides, HA treatment induced migration towards HA of MDR cell lines through Tiam1 activation by a PI3K-dependent mechanism, showing that disruption of HA signaling would be useful in treatment of MDR hematological malignancies. Fil: Cordo Russo, Rosalia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina Fil: Alaniz, Laura Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas. Laboratorio de Terapia Genética; Argentina Fil: Saccodossi, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina Fil: Lompardía, Silvina Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina Fil: Blanco, Guillermo Armando C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina Fil: Alvarez Carbonetto, Elida M. del C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina Fil: García, Mariana Gabriela. Universidad Austral. Facultad de Ciencias Biomédicas. Laboratorio de Terapia Genética; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina Fil: Hajos, Silvia Elvira. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina

Published
2010
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2. Inhibition of NF-κB activity by BAY 11-7082 increases apoptosis in multidrug resistant leukemic T-cell lines

Author

Laura Alaniz, Guillermo A. Blanco, Mariana Garcia, Elida Alvarez, Eloisi Caldas Lopes, and Silvia E. Hajos

Subjects
Cancer Research, Programmed cell death, Leukemia, T-Cell, Daunorubicin, T cell, Apoptosis, Biology, medicine.disease_cause, Mice, Cell Line, Tumor, Nitriles, medicine, Animals, Cytotoxic T cell, Doxorubicin, Sulfones, NF-kappa B p50 Subunit, Hematology, Molecular biology, Drug Resistance, Multiple, Multiple drug resistance, medicine.anatomical_structure, Gene Expression Regulation, Oncology, Vincristine, Cytokines, Carcinogenesis, medicine.drug
Abstract

Multidrug resistance (MDR) is the main reason for failure of cancer therapy with resistance to apoptosis being one of the mechanisms involved. Constitutive NF-kappaB activity has been detected in many tumors contributing to oncogenesis and tumor survival whereas inhibition of NF-kappaB activity has proved to enhance cell death induced by chemotherapeutic agents. Consequently, the use of BAY 11-7082, an irreversible inhibitor of IkappaB-alpha phosphorylation, could be beneficial in the treatment of certain tumors. Although there are several reports which demonstrate a transient activation of NF-kappaB by cytotoxic drugs, little is known about the role of NF-kappaB activation in the development of a chemoresistant phenotype in leukemic cells. In this study, we analyzed the relationship between NF-kappaB and the survival of murine leukemic drug resistant cell lines. The modulation of this transcription factor by BAY 11-7082 and the chemotherapeutic agents vincristine and doxorubicin was evaluated. The effect of BAY 11-7082 on the expression of genes containing NF-kappaB-binding sites was also studied. We found that the cell lines LBR-V160 and LBR-D160 (resistant to vincristine and doxorubicin, respectively) presented higher constitutive NF-kappaB activity than the sensitive LBR- and the active complex contained both p50 and p65 subunits. BAY 11-7082 (3.5 microM) inhibited constitutive NF-kappaB activity in the three cell lines whereas the anticancer agents did not. Treatment with BAY 11-7082 induced a higher percentage of apoptosis in LBR-V160 and LBR-D160 than in LBR-. Cells treated with BAY 11-7082 displayed modulation of NF-kappaB-inducible genes such as IL-10, IL-15, TNF-alpha and TGF-beta. Taken together, these data suggest that suppression of constitutive NF-kappaB activity by BAY 11-7082 may be a useful treatment for MDR leukemias.

Published
2005
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3. PI3K/Akt inhibition modulates multidrug resistance and activates NF-kappaB in murine lymphoma cell lines

Author

Rosalia I. Cordo Russo, Silvia E. Hajos, Mariana Garcia, Laura Alaniz, and Elida Ester Alvarez

Subjects
Cancer Research, CIENCIAS MÉDICAS Y DE LA SALUD, Lymphoma, Down-Regulation, PI3K, Wortmannin, chemistry.chemical_compound, Mice, PgP, Cell Line, Tumor, MDR, LYMPHOMA, Animals, LY294002, Phosphatidylinositol, ATP Binding Cassette Transporter, Subfamily B, Member 1, Protein kinase B, PI3K/AKT/mTOR pathway, P-glycoprotein, Phosphoinositide-3 Kinase Inhibitors, biology, Chemistry, NF-kappa B, Hematology, Bioquímica y Biología Molecular, Drug Resistance, Multiple, DRUG RESISTANCE, Multiple drug resistance, Medicina Básica, Oncology, Apoptosis, Doxorubicin, Vincristine, biology.protein, Cancer research, Proto-Oncogene Proteins c-akt
Abstract

Upregulation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway has been described in some tumors related to multidrug resistance (MDR). The aim of this work was to analyze the relationship between PI3K/Akt, MDR and NF-kappaB in murine lymphoma cell lines resistant to vincristine (LBR-V160) and doxorubicin (LBR-D160) as well as in the sensitive line (LBR-). PI3K/Akt activity, analyzed by phosphatidylinositol trisphosphate production and phosphorylated Akt (p-Akt) expression, was higher in the resistant cell lines than in the sensitive one and inhibition with wortmannin or LY294002 improved apoptosis in the resistant cell lines. Vincristine but not doxorubicin increased p-Akt expression whereas co-treatment with PI3K inhibitors and vincristine increased apoptosis in the three cell lines. Wortmannin and LY294002 inhibited P-glycoprotein (Pgp) function and also increased NF-kappaB activity. We concluded that the PI3K/Akt pathway is involved in MDR in lymphoma cell lines and PI3K/Akt inhibition correlates down-regulation of NF-kappaB activity and inhibition Pgp function. Fil: García, Mariana Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina Fil: Alaniz, Laura Daniela. Universidad Austral. Facultad de Ciencias Biomédicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Cordo Russo, Rosalia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina Fil: Alvarez, Elida Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina Fil: Hajos, Silvia Elvira. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina

Published
2008

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