Pravastatin induces cell cycle arrest and decreased production of VEGF and bFGF in multiple myeloma cell line

Multiple myeloma (MM) is a B cell bone marrow neoplasia characterized by inflammation with an intense secretion of growth factors that promote tumor growth, cell survival, migration and invasion. The aim of this study was to evaluate the effects of pravastatin, a drug used to reduce cholesterol, in a MM cell line.Cell cycle and viability were determinate by Trypan Blue and Propidium Iodide. IL6, VEGF, bFGF and TGFβ were quantified by ELISA and qRT-PCR including here de HMG CoA reductase. It was observed reduction of cell viability, increase of cells in G0/G1 phase of the cell cycle and reducing the factors VEGF and bFGF without influence on 3-Methyl-Glutaryl Coenzyme A reductase expression.The results demonstrated that pravastatin induces cell cycle arrest in G0/G1 and decreased production of growth factors in Multiple Myeloma cell line.

Keywords:
pravastatin; Multiple Myeloma; 3-Methyl-Glutaryl Coenzyme A reductase; vascular endothelial growth factor; fibroblast growth factor

Authorship

P. J. J. Trojan

Laboratório Multidisciplinar de Ciências Biológicas e da Saúde, Universidade Estadual de Ponta Grossa – UEPG, Campus de Uvaranas, Av. General Carlos Cavalcanti, 4748, CEP 84030-900, Ponta Grossa, PR, BrazilUniversidade Estadual de Ponta GrossaBrazilPonta Grossa, PR, BrazilLaboratório Multidisciplinar de Ciências Biológicas e da Saúde, Universidade Estadual de Ponta Grossa – UEPG, Campus de Uvaranas, Av. General Carlos Cavalcanti, 4748, CEP 84030-900, Ponta Grossa, PR, Brazil

M. S. Bohatch-Junior

M. F. Otuki

Departamento de Ciências Farmacêuticas, Universidade Estadual de Ponta Grossa – UEPG, Campus de Uvaranas, Av. General Carlos Cavalcanti, 4748, CEP 84030-900, Ponta Grossa, PR, BrazilUniversidade Estadual de Ponta GrossaBrazilPonta Grossa, PR, BrazilDepartamento de Ciências Farmacêuticas, Universidade Estadual de Ponta Grossa – UEPG, Campus de Uvaranas, Av. General Carlos Cavalcanti, 4748, CEP 84030-900, Ponta Grossa, PR, Brazil

F. Souza-Fonseca-Guimarães

Unit Cytokines and Inflammation, Department Infection and Epidemiology Institut Pasteur, 25-28 rue du Docteur Roux, 75015, Paris, FranceDepartment Infection and Epidemiology Institut PasteurFranceParis, FranceUnit Cytokines and Inflammation, Department Infection and Epidemiology Institut Pasteur, 25-28 rue du Docteur Roux, 75015, Paris, France

P. V. Svidnicki

Laboratório de Citogenética e Evolução, Departamento de Biologia Molecular, Estrutural e Genética, Universidade Estadual de Ponta Grossa – UEPG, Campus de Uvaranas, Av. General Carlos Cavalcanti, 4748, CEP 84030-900, Ponta Grossa, PR, BrazilUniversidade Estadual de Ponta GrossaBrazilPonta Grossa, PR, BrazilLaboratório de Citogenética e Evolução, Departamento de Biologia Molecular, Estrutural e Genética, Universidade Estadual de Ponta Grossa – UEPG, Campus de Uvaranas, Av. General Carlos Cavalcanti, 4748, CEP 84030-900, Ponta Grossa, PR, Brazil

V. Nogaroto

D. Fernandes

E. A. Krum

G. M. Favero ^**e-mail: gmfavero@uepg.br

*e-mail: gmfavero@uepg.br

SCIMAGO INSTITUTIONS RANKINGS

Figures

Figures (4)

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Figure 1
Pravastatin reduces the number of viable cells in cultured Multiple Myeloma after 72 hours . Cells were cultured in the presence of the pravastatin, or vehicle for 3 days. Three wells of each condition were subjected to the Trypan Blue assay. Data are expressed as mean and standard error of the mean. Statistical analysis was performed using ANOVA followed by Bonferroni´s Multiple Comparison Test. * p < 0.05 compared with the control group.

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Figure 2
Pravastatin induces G0/G1 cell cycle arrest . Flow cytometry Cell cycle analysis, using propidium iodide. (a) Percentage of cell in G0/G1 phase; (b) Percentage of cells in Synthesis Phase; (c) Cells on G2/M Phases. Each bar represents the mean and standard error of the mean of a representative assay performed three times in triplicate. The first bars are 24h, the second 48h and the third bar 72h. (ANOVA followed by Bonferroni´s Multiple Comparison Test).

Thumbnail

Figure 3
Pravastatin induces the loss of VEGF and FGF . Evaluation of different factors in the supernatant culture of MM treated with Pravastatin in different concentrations (ELISA assay). The result shown is representative of 48h of treatment in triplicate. Each bar represents the mean with their standard deviations. Statistical analysis was performed using Student’s t-test. * p < 0.05 compared with the control group.

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Figure 4
Pravastatin not change the expression of HMG CoA reductase . Evaluation of different mRNA by qRT PCR. The result shown is representative of 48h of treatment performed three times in triplicate. Threshold cycle (Ct) was measured and a relative change in the expression level of one specific gene was presented as 2^−ΔΔCt Each bar represents the mean with their standard deviations. Statistical analysis was performed using Student’s t-test. * p < 0.05 compared with the control group.

Figure 1 Pravastatin reduces the number of viable cells in cultured Multiple Myeloma after 72 hours . Cells were cultured in the presence of the pravastatin, or vehicle for 3 days. Three wells of each condition were subjected to the Trypan Blue assay. Data are expressed as mean and standard error of the mean. Statistical analysis was performed using ANOVA followed by Bonferroni´s Multiple Comparison Test. * p < 0.05 compared with the control group.

Figure 2 Pravastatin induces G0/G1 cell cycle arrest . Flow cytometry Cell cycle analysis, using propidium iodide. (a) Percentage of cell in G0/G1 phase; (b) Percentage of cells in Synthesis Phase; (c) Cells on G2/M Phases. Each bar represents the mean and standard error of the mean of a representative assay performed three times in triplicate. The first bars are 24h, the second 48h and the third bar 72h. (ANOVA followed by Bonferroni´s Multiple Comparison Test).

Figure 3 Pravastatin induces the loss of VEGF and FGF . Evaluation of different factors in the supernatant culture of MM treated with Pravastatin in different concentrations (ELISA assay). The result shown is representative of 48h of treatment in triplicate. Each bar represents the mean with their standard deviations. Statistical analysis was performed using Student’s t-test. * p < 0.05 compared with the control group.

Figure 4 Pravastatin not change the expression of HMG CoA reductase . Evaluation of different mRNA by qRT PCR. The result shown is representative of 48h of treatment performed three times in triplicate. Threshold cycle (Ct) was measured and a relative change in the expression level of one specific gene was presented as 2^−ΔΔCt Each bar represents the mean with their standard deviations. Statistical analysis was performed using Student’s t-test. * p < 0.05 compared with the control group.

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Pravastatin induces cell cycle arrest and decreased production of VEGF and bFGF in multiple myeloma cell line

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[1] *e-mail: gmfavero@uepg.br