Importance of Detecting Multidrug Resistance Proteins in Acute Leukemia Prognosis and Therapy

Moraes, Ana Carolina Rabello de; Maranho, Caroline Klein; Rauber, Gabriela Schneider; Santos-Silva, Maria Cláudia

doi:10.1002/jcla.21563

Cited by 25 publications

(41 citation statements)

References 89 publications

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“…Intracellular L-lactate induces the expression of one or more of the reversible monocarboxylate/proton symporters MCT1, MCT2, MCT3, MCT4, and/or SMCT1, which allow L-lactate to exit cancer cells. Fortunately, 3-BP is a polar compound and is thus not a substrate for the multiple-drug resistance network, which inactivates many anticancer drugs in mammals [39,40]. As 3-BP is an alkylating agent, it pyruvylates and inactivates the SH group of accessible cysteine residues [37].…”

Section: Discussionmentioning

confidence: 99%

Killing multiple myeloma cells with the small molecule 3-bromopyruvate

et al. 2014

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The small molecule 3-bromopyruvate (3-BP), which has emerged recently as the first member of a new class of potent anticancer agents, was tested for its capacity to kill multiple myeloma (MM) cancer cells. Human MM cells (RPMI 8226) begin to lose viability significantly within 8 h of incubation in the presence of 3-BP. The Km (0.3 mmol/l) for intracellular accumulation of 3-BP in MM cells is 24 times lower than that in control cells (7.2 mmol/l). Therefore, the uptake of 3-BP by MM cells is significantly higher than that by peripheral blood mononuclear cells. Further, the IC50 values for human MM cells and control peripheral blood mononuclear cells are 24 and 58 µmol/l, respectively. Therefore, specificity and selectivity of 3-BP toward MM cancer cells are evident on the basis of the above. In MM cells the transcription levels of the gene encoding the monocarboxylate transporter MCT1 is significantly amplified compared with control cells. The level of intracellular ATP in MM cells decreases by over 90% within 1 h after addition of 100 µmol/l 3-BP. The cytotoxicity of 3-BP, exemplified by a marked decrease in viability of MM cells, is potentiated by the inhibitor of glutathione synthesis buthionine sulfoximine. In addition, the lack of mutagenicity and its superior capacity relative to Glivec to kill MM cancer cells are presented in this study.

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Section: Discussionmentioning

confidence: 99%

Killing multiple myeloma cells with the small molecule 3-bromopyruvate

et al. 2014

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“…Chekhun et al, (2006) reported the relationship between MDR1 promoter methylation and drug resistance in the T-cell line as well as three patients with chronic lymphocytic leukemia. Expression of P-gp is the main barrier in chemotherapy for hematological malignancies, including acute myeloid leukemia (Mahadevan and List, 2004;Chekhun et al, 2006;de Moraes et al, 2013;Gao et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Regulatory Effect of Resveratrol and Prednisolone on MDR1 Protein Expression in Acute Lymphoblastic Leukemia Cell Line (CCRF-CEM)

Talebi

Aghdam

Azimi

et al. 2019

Asian Pac J Cancer Prev

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“…The cell lysates were prepared (10 μg/lane) and separated on 10% SDS‐polyacrylamide gel and then transferred to nitrocellulose membranes. The membranes were incubated sequentially with mouse monoclonal anti‐P‐gp or anti‐β‐actin antibody (1:10,000) and HRP‐conjugated mouse anti‐mouse IgG (1:10,000) .…”

Section: Methodsmentioning

confidence: 99%

Reversal of Human Multi‐Drug Resistance Leukaemic Cells by Stemofoline Derivatives via Inhibition of P‐Glycoprotein Function

Umsumarng

Pitchakarn

Sastraruji

et al. 2014

Basic Clin Pharma Tox

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Our previous study reported multi-drug resistance (MDR) reversing properties of synthetic stemofoline derivatives (STFD), OH-A1, NH-B6 and NH-D6 on P-glycoprotein (P-gp) overexpressing leukaemic cells (K562/Adr); however, the mechanism was unclear. In this study, we further investigated whether the STFD reverse MDR through either the inhibition of P-gp function or expression in K562/Adr cells, or both. The P-gp functional studies showed that the STFD increased the accumulation of calcein-AM, rhodamine 123 and [14 C]-doxorubicin in K562/Adr cells, while the effects have not been seen in their parental sensitive cancer cell line (K562). Further, the STFD did not alter the P-gp expression as determined by Western blotting. This study concludes that the STFD reverse MDR via the inhibition of P-gp function. The efficacy of the STFD to inhibit P-gp function followed the order: NH-B6 > OH-A1 > NH-D6. These compounds could be introduced as candidate molecules for treating cancers exhibiting P-gp-mediated MDR.

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Importance of Detecting Multidrug Resistance Proteins in Acute Leukemia Prognosis and Therapy

Cited by 25 publications

References 89 publications

Killing multiple myeloma cells with the small molecule 3-bromopyruvate

Killing multiple myeloma cells with the small molecule 3-bromopyruvate

Regulatory Effect of Resveratrol and Prednisolone on MDR1 Protein Expression in Acute Lymphoblastic Leukemia Cell Line (CCRF-CEM)

Reversal of Human Multi‐Drug Resistance Leukaemic Cells by Stemofoline Derivatives via Inhibition of P‐Glycoprotein Function

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