Coexpression of p53 protein and MDR functional phenotype in leukemias: The predominant association in chronic myeloid leukemia

Cavalcanti, Geraldo Barroso; Vasconcelos, Flavia da Cunha; Faria, Giselle Pinto de; Scheiner, Marcos Antônio Maurício; Dobbin, Jane; Klumb, Claudete Esteves; Maia, Raquel Ciuvalschi

doi:10.1002/cyto.b.20013

Cited by 22 publications

(23 citation statements)

References 42 publications

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“…Results were expressed as ratio of MFI of MRP1 or p53. Samples were considered p53 positive when MFI ratio≥1.4 [27], and were considered MRP1 positive when MFI ratio≥1.1 [23]. Cells were then permeabilized using a FACS lysing solution, washed in 0.5% Tween-20/PBS, and incubated with 1% BSA (bovine serum albumin, Sigma-Aldrich, St. Louis, USA).…”

Section: Determination Of Mrp1 and P53 Expression By Flow Cytometrymentioning

confidence: 99%

LQB-118, a pterocarpanquinone structurally related to lapachol [2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone]: a novel class of agent with high apoptotic effect in chronic myeloid leukemia cells

et al. 2010

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Despite the relevant therapeutic progresses obtained with imatinib, clinical resistance to this drug has emerged and reemerged after cytogenetic remission in a group of patients with chronic myeloid leukemia (CML). Therefore, novel treatment strategies are needed. In this study, we evaluated the anti-CML activity and mechanisms of action of LQB-118, a pterocarpanquinone structurally related to lapachol [2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone]. LQB-118 treatment resulted in an important reduction of cell viability in cell lines derived from CML, both the vincristine-sensitive K562 cell line, and the resistant K562-Lucena (a cell line overexpressing P-glycoprotein). In agreement with these results, the induction of caspase-3 activation by this compound indicated that a significant rate of apoptosis was taking place. In these cell lines, apoptosis induced by LQB-118 was accompanied by a reduction of P-glycoprotein, survivin, and XIAP expression. Moreover, this effect was not restricted to cell lines as LQB-118 produced significant apoptosis rate in cells from CML patients exhibiting multifactorial drug resistance phenotype such as P-glycoprotein, MRP1 and p53 overexpression. The data suggest that LQB-118 has a potent anti-CML activity that can overcome multifactorial drug resistance mechanisms, making this compound a promising new anti-CML agent.

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Section: Determination Of Mrp1 and P53 Expression By Flow Cytometrymentioning

confidence: 99%

LQB-118, a pterocarpanquinone structurally related to lapachol [2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone]: a novel class of agent with high apoptotic effect in chronic myeloid leukemia cells

et al. 2010

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“…Based on cutoff point previously adopted by us in our work [19,20], the expression of p53 was observed in five out of 20 (25%), Pgp expression in 16 out of 19 (84%) and MRP expression in 15 out of 20 (75%) of the samples. MRP and Pgp co-expression was found in 11 out of 19 (57.9%) samples.…”

Section: Mdr Phenotype In CML Patientsmentioning

confidence: 99%

Pomolic acid-induced apoptosis in cells from patients with chronic myeloid leukemia exhibiting different drug resistance profile

et al. 2007

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Pomolic acid (PA) is a pentacyclic triterpene which has been previously described as active in inhibiting the growth of K562 cell line-originated from chronic myeloid leukemia (CML) in blast crisis-and its vincristine-resistant derivative K562-Lucena1. In this work, cells from CML patients were treated with PA and the apoptotic index was compared with the multidrug resistance (MDR) profile and clinical status of the patients. Our findings show that PA 12.5 microg/ml at 24 h (p = 0.000), at 48 h (p = 0.012) and at 72 h (p = 0.005) has a potent apoptotic index in CML cells as compared to mononuclear cells from healthy donors. PA was capable to induce apoptosis in cells from CML patients exhibiting functional MDR phenotype but not in P-glycoprotein expression. In addition, PA was effective in chronic as well as in blast phase of CML. Moreover, similar apoptotic index induced by PA was observed in low, intermediate and high-risk Sokal score as well as in samples from the group of patients with clinical resistance to interferon and/or imatinib and non-treated patients. These results suggest that PA may be an effective agent for the treatment of CML.

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“…p53 protein expression was determined in all samples with MoAb clone DO-7, which recognizes an epitope at the N-terminus of the human p53 protein and reacts with both wild-type and mutant proteins (12,23).…”

Section: Detection Of P53 Protein Expression In Patients and Controlsmentioning

confidence: 99%

p53 flow cytometry evaluation in leukemias: Correlation to factors affecting clinical outcome

Cavalcanti

Scheiner

Magluta

et al. 2010

Cytometry Part B Clinical

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p53 is a cell cycle checkpoint control protein that assesses DNA damage and acts as a transcription factor regulating genes, which control cell growth, DNA repair, and apoptosis. p53 mutations have been found in a wide variety of different cancers including flow cytometric assessment of p53 protein expression using anti-p53 monoclonal antibodies. We studied p53 protein expression by flow cytometry (

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Coexpression of p53 protein and MDR functional phenotype in leukemias: The predominant association in chronic myeloid leukemia

Cited by 22 publications

References 42 publications

LQB-118, a pterocarpanquinone structurally related to lapachol [2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone]: a novel class of agent with high apoptotic effect in chronic myeloid leukemia cells

LQB-118, a pterocarpanquinone structurally related to lapachol [2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone]: a novel class of agent with high apoptotic effect in chronic myeloid leukemia cells

Pomolic acid-induced apoptosis in cells from patients with chronic myeloid leukemia exhibiting different drug resistance profile

p53 flow cytometry evaluation in leukemias: Correlation to factors affecting clinical outcome

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