scholarly journals Reversal in multidrug resistance by magnetic nanoparticle of Fe3O4 loaded with adriamycin and tetrandrine in K562/A02 leukemic cells

2008 ◽  
pp. 277
Author(s):  
Sun
Keyword(s):  
Multidrug Resistance ◽  
Magnetic Nanoparticle ◽  
Leukemic Cells

Mechanism Research of Magnetic Nanoparticle Fe3O4 and 5-Bromotetrandrine On Reversal of Multidrug Resistance in K562/A02 Leukemic Cells.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4827-4827
Author(s):  
Bao-An Chen ◽  
Wei-Wei Wu ◽  
Jian Cheng ◽  
Feng Gao ◽  
Wen-Lin Xu ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Cell Line ◽  
Magnetic Nanoparticle ◽  
Conflicts Of Interest ◽  
Synergetic Effect ◽  
Leukemic Cells ◽  
Reversal Agents ◽  
Mechanism Research ◽  
Magnetic Nanoparticles Fe3o4 ◽  
Fe3o4 Mnps

Abstract Abstract 4827 Purpose The present study aimed to research the machenism of magnetic nanoparticles Fe3O4 (Fe3O4-MNPs) and 5-bromotetrandrine (BrTet) on multidrug resistance cell line K562/A02 solitarily or symphysially. Mothed The proliferation of K562 and K562/A02 cells, and the cytotoxicity of PMBCs which were cultured with daunomycin (DNR) alone or in combination with Fe3O4-MNPs (0.1, V/V), BrTet (0.5μM) or both for 48 h, were evaluated by MTT assay. DNR accumulation of K562, K562/A02 cells and PMBCs were analyzed by fluorospectrophotometry after incubated with 2μM DNR in the absence or presence with Fe3O4-MNPs (0.1 V/V), BrTet (0.5μM) or both for 48 h. Real time–PCR analyses and western blotting were performed to examine the mRNA and proteins level, respectively. Result The results showed that the combination of Fe3O4-MNPs and BrTet with effective concentration could exaggerate cytotoxicity against MDR cell line K562/A02 significantly. Flow cytometry assay showed that 0.5μM BrTet in combination with Fe3O4-MNPs (0.1, V/V) significantly enhanced the intracellular accumulation of DNR in K562/A02 cells and its potency was greater than that of BrTet or Fe3O4-MNPs alone at the same concentrations. While both Fe3O4-MNPs and BrTet in company with DNR did not increase the cytotoxicity to PMBCs. Both BrTet and Fe3O4-MNPs inhibited the overexpression of MRP1, MRP2, MRP4 and MRP5, and down regulated, mrps mRNA expression in K562/A02 cells to some extent. Conclusion We propose that Fe3O4-MNPs loaded with DNR and BrTet probably have synergetic effect on reversal in multidrug resistance. However, this combination shows less cytotoxicity to normal cells and reveals better target. The results may provide evidence for clinic application of them as reversal agents of drug resistance. Disclosures No relevant conflicts of interest to declare.

scholarly journals Selective Cytotoxicity of Piperine over Multidrug Resistance Leukemic Cells

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 934
Author(s):  
Julia Quarti ◽  
Daianne N. M. Torres ◽  
Erika Ferreira ◽  
Raphael S. Vidal ◽  
Fabiana Casanova ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Black Pepper ◽  
Leukemic Cells ◽  
Glycoprotein P ◽  
Cytotoxic Effects ◽  
Collateral Sensitivity ◽  
Main Challenge ◽  
Independent Mechanism ◽  
High Level ◽  
Parp 1

Multidrug resistance (MDR) is the main challenge in the treatment of chronic myeloid leukemia (CML), and P-glycoprotein (P-gp) overexpression is an important mechanism involved in this resistance process. However, some compounds can selectively affect MDR cells, inducing collateral sensitivity (CS), which may be dependent on P-gp. The aim of this study was to investigate the effect of piperine, a phytochemical from black pepper, on CS induction in CML MDR cells, and the mechanisms involved. The results indicate that piperine induced CS, being more cytotoxic to K562-derived MDR cells (Lucena-1 and FEPS) than to K562, the parental CML cell. CS was confirmed by analysis of cell metabolic activity and viability, cell morphology and apoptosis. P-gp was partially required for CS induction. To investigate a P-gp independent mechanism, we analyzed the possibility that poly (ADP-ribose) polymerase-1 (PARP-1) could be involved in piperine cytotoxic effects. It was previously shown that only MDR FEPS cells present a high level of 24 kDa fragment of PARP-1, which could protect these cells against cell death. In the present study, piperine was able to decrease the 24 kDa fragment of PARP-1 in MDR FEPS cells. We conclude that piperine targets selectively MDR cells, inducing CS, through a mechanism that might be dependent or not on P-gp.

scholarly journals Antiproliferative and Apoptosis-Inducing Activities of Benchalokawichian Remedy Against Doxorubicin-Sensitive and -Resistant Erythromyelogenous Leukemic Cells

2021 ◽  
Vol 20 (3) ◽  
Author(s):  
Wipob Suttana ◽  
Chatubhong Singharachai ◽  
Rawiwan Charoensup ◽  
Narawadee Rujanapun ◽  
Chutima Suya
Keyword(s):  
Cell Cycle ◽  
Multidrug Resistance ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
K562 Cells ◽  
Leukemic Cells ◽  
Drug Resistant ◽  
Normal Cells ◽  
Root Extracts ◽  
Cycle Arrest

Chemotherapy can cause multidrug resistance in cancer cells and is cytotoxic to normal cells. Discovering natural bioactive compounds that are not cytotoxic to normal cells but inhibit proliferation and induce apoptosis in drug- sensitive and drug-resistant cancer cells could overcome these drawbacks of chemotherapy. This study investigated the antiproliferative effects of crude extracts of Benchalokawichian (BLW) remedy and its herbal components against drug-sensitive and drug-resistant cancer cells, cytotoxicity of the extracts toward normal cells, and their ability to induce apoptosis and cell cycle arrest in drug-sensitive and drug-resistant cancer cells. The extracts exhibited antiproliferative activity against doxorubicin-sensitive and doxorubicin-resistant erythromyelogenous leukemic cells (K562 and K562/adr). Tiliacora triandra root, BLW, and Harrisonia perforata root extracts displayed an IC50 of 77.00 ± 1.30, 79.33 ± 1.33, and 87.67 ± 0.67 µg/mL, respectively, against K562 cells. In contrast, Clerodendrum petasites, T. triandra, and H. perforata root extracts displayed the lowest IC50 against K562/adr cells (68.89 ± 0.75, 78.33 ± 0.69, and 86.78 ± 1.92 µg/mL, respectively). The resistance factor of the extracts was lower than that of doxorubicin, indicating that the extracts could overcome the multidrug resistance of cancer cells. Importantly, the extracts were negligibly cytotoxic to peripheral mononuclear cells, indicating minimal adverse effects in normal cells. In addition, these extracts induced apoptosis of K562 and K562/adr cells and caused cell cycle arrest at the G0/G1 phase in K562 cells. Keywords: Antiproliferative, Apoptosis, Benchalokawichian, Cell cycle, Multidrug resistance

scholarly journals Immunophenotyping Investigation of Minimal Residual Disease Is a Useful Approach for Predicting Relapse in Acute Myeloid Leukemia Patients

Blood ◽  
1997 ◽  
Vol 90 (6) ◽  
pp. 2465-2470 ◽  
Author(s):  
J.F. San Miguel ◽  
A. Martı́nez ◽  
A. Macedo ◽  
M.B. Vidriales ◽  
C. López-Berges ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Multidrug Resistance ◽  
Minimal Residual Disease ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Leukemic Cells ◽  
Rhodamine 123 ◽  
Minimal Residual ◽  
Acute Myeloid

Abstract A high complete remission rate is currently achieved in patients with acute myeloid leukemia (AML). However, many patients eventually relapse due to the persistence of low numbers of residual leukemic cells that are undetectable by conventional cytomorphologic criteria (minimal residual disease [MRD]). Using immunophenotypic multiparametric flow cytometry, we have investigated in sequential studies (diagnosis and follow-up) the impact of MRD detection on the outcome of 53 AML patients that had achieved morphologic remission with standard AML protocols and displayed at diagnosis an aberrant phenotype. Patients were studied at diagnosis with a panel of 35 monoclonal antibodies in triple staining combinations for detection of aberrant or uncommon phenotypic features. According to these features, a patient's probe was custom-built at diagnosis for the identification of possible residual leukemic cells during follow-up. The level of MRD at the end of induction and intensification therapy correlated with the number of relapses and relapse-free survival (RFS). Thus, patients with more than 5 × 10−3 residual cells (5 residual cells among 1,000 normal bone marrow [BM] cells) identified as leukemic by immunophenotyping in the first remission BM showed a significant higher rate of relapse (67% v 20% for patients with less than 5 × 10−3 residual cells; P = .002) and a lower median RFS (17 months v not reached; P = .01). At the end of intensification, with a cut-off value of 2 × 10−3 leukemic cells, AML patients also separated into two distinct groups with relapse rates of 69% versus 32% (P = .02), respectively, and median RFS of 16 months versus not reached (P = .04). In addition, overall survival was also significantly related to the level of residual cells in the marrow obtained at the end of induction and particularly after intensification therapy (P = .008). Furthermore, we have explored whether residual disease was related with the functional expression of multidrug resistance (MDR-1) at diagnosis as assessed by the rhodamine-123 assay. Patients with ≥5 × 10−3 residual leukemic cells at the end of induction therapy had a significantly higher rhodamine-123 efflux (mean, 56% ± 24%) than those with less than 5 × 10−3 residual cells (mean, 32% ± 31%; P = .04). Finally, multivariate analysis showed that the number of residual cells at the end of induction or intensification therapy was the most important prognostic factor for prediction of RFS. Overall, our results show that immunophenotypical investigation of MRD strongly predicts outcome in patients with AML and that the number of residual leukemic cells correlates with multidrug resistance.

Reversal of Multidrug Resistance by Magnetic Fe3O4 Nanoparticle Copolymerizating Daunorubicin and mdr1-shRNA Expression Vetor in Leukemia Cells.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4829-4829
Author(s):  
Bao-An Chen ◽  
Peipei Mao ◽  
Jian Cheng ◽  
Feng Gao ◽  
Jia-Hua Ding ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Cell Line ◽  
Recombinant Plasmid ◽  
Conflicts Of Interest ◽  
Transfection Efficiency ◽  
Resistance Index ◽  
Leukemic Cells ◽  
Target Sequence ◽  
Shrna Expression ◽  
Mdr 1

Abstract Abstract 4829 Object In many instances, Multidrug resistance (MDR) is mediated by increased expression at the cell surface of the MDR1 gene product, P-glycoprotein (P-gp), a 170-kD energy-dependent efflux pump. The aim of this study was to investigate the potential benefit of combination therapy with magnetic nanoparticle of Fe3O4 (MNP(Fe3O4)) and mdr1-shRNA Expression vetor.in K562/A02 leukemic cells. Methods To synthesis short hairpin RNA (shRNA)aiming divectly at the target sequence,we choice the 3491-3509,1539-1557and 3103-3121 nucleotide of mdr-1 mRNA as targets. Cloning in the plasmid vetor PGCSilencer-U6-neo-GFP, The recombinant plasmid vetors were called for PGY1-1,PGY1-2 and PGY1-3.The recombinant plasmid vetors were transfected into the cell 1ines K562/A02 by lipofection. After transfected 48 hours,the inhibition of mdr-1mRNA expression and the expression of P-gp was detected by realtime–PCR and Weston-blot, screening the recombinant plasmid vetor which has the most greatest mdr-1 gene inhibition ratio is PGY1-2.Analysis of the reveral ratio of multidrug resistance, the concentration of DNR and the content of mdr-1 gene and P-gp in K562/A02 cell line. Results The combination of daunorubicin (DNR) with either MNP(Fe3O4) or PGY1-2 exerted a potent cytotoxic effect on K562/A02 cells, while MNP(Fe3O4) and PGY1-2 cotreatment can synergistically down regulation the expression of mdr-1 gene and the expression of P-gp(P<0.05). The transfection efficiency was 20%; the concentration of DNR in K562/A02 cell line was obviously elevated (P<0.05);the multidrug resistance index of K562/A02 cell line was obviously decreased (P<0.05). Conclusion MNP(Fe3O4) and PGY1-2 cotreatment can synergistically reveral multidrug resistance. Thus our in vitro data strongly suggests a potential clinical application of MNP(Fe3O4) and PGY1-2 combination on CML. Disclosures No relevant conflicts of interest to declare.

Induced Apoptosis Of Multidrug Resistance Leukemia K562/A02 Cells By Magnetic Nanoparticle Of Fe3O4 Copolymerizating JNK1 shRNA Expression Vector and Daunorubicin

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4925-4925
Author(s):  
Wei Zhang ◽  
Baoan Chen ◽  
Xiangfeng He ◽  
Rong Fu
Keyword(s):  
Multidrug Resistance ◽  
Protein Level ◽  
Magnetic Nanoparticle ◽  
Expression Vector ◽  
Caspase 3 ◽  
Chromatin Condensation ◽  
Dapi Staining ◽  
Shrna Expression ◽  
Chemotherapeutic Regimen ◽  
Shrna Expression Vector

Abstract Currently, serious toxicity and poor antitumor efficacy resulting from the induction of multidrug resistance (MDR) in hematological malignancies and solid tumors are common hindrances to successful systemic chemotherapy. One of the important mechanisms of tumorigenesis and resistance to anticancer drugs was blockade of the apoptosis-inducing pathway. In order to overcome tumor MDR while maintaining good antitumor activity, biomaterial combine with gene therapy provides a novel strategy for the treatment of MDR.The aim of this study was to explore the induction of apoptosis by magnetic nanoparticle of Fe3O4 (MNPs-Fe3O4), a novel delivery system for chemotherapeutic regimen that is chemically stable, environmentally friendly, and noncytotoxic, copolymerizating JNK1shRNA expression vector with DNR, which could overcome siRNA technique instability and enhance DNR chemotherapeutic efficiency and provide a new field to reverse tumor MDR. JNK1shRNA expression vector was constructed and screened the most effective plasmid and transfected the cells. Typical apoptotic characteristics and apoptosis effect of MNPs-Fe3O4 and PGM-3 with DNR were investigated by DAPI staining and FCM assay, respectively. Additionally, drug accumulation and apoptosis relative-genes were evaluated in K562/AO2 leukemia cells.The results showed that PGCsilencer-U6-neo-GFP-GV102 shRNA/JNK1 was successfully constructed, which was confirmed by sequencing that expression of JNK1 gene in mRNA and protein level that had the less in PGM-3 than that of PGM-1 or PGM-2. Meanwhile, MNPs-Fe3O4 and PGM-3 with DNR (DNR/PGM-3/MNPs-Fe3O4) could synergistically induced typical apoptotic characteristics of chromatin condensation and apoptotic body with DAPI staining, and a higher rate of apoptosis were detected in K562/A02 cells treated with DNR/PGM-3/MNPs-Fe3O4. Intracellular DNR was higher in K562/A02 cells treated with DNR/PGM-3/MNPs-Fe3O4 than that of DNR/MNPs-Fe3O4 by FCM analysis.  Further study demonstrated that both DNR/PGM-3/MNPs-Fe3O4 and DNR/PGM-3 reduced the gene transcriptions and protein expressions of bcl-2, enhanced that of bax and caspase-3, decreased survivin in protein level, and has no different change in mRNA level by qRT-PCR and Western blotting analyses, respectively. These findings showed that the combination of MNPs-Fe3O4 with JNK1 shRNA expression vector and DNR could induce apoptosis of K562/A02 cells through elevating the ratio of bax/bcl-2, activating caspase-3, and decreasing survivin in protein level. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Multidrug resistance P-glycoprotein expression on leukemic cells at diagnosis.

1997 ◽  
Vol 36 (3) ◽  
pp. 299-304
Author(s):  
Hiroyasu KAYA ◽  
Shinobu NAKAMURA ◽  
Tsunehisa IKENO ◽  
Noritaka HATTORI ◽  
Minoru TAKESHIMA ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Leukemic Cells ◽  
P Glycoprotein

scholarly journals Immunophenotyping Investigation of Minimal Residual Disease Is a Useful Approach for Predicting Relapse in Acute Myeloid Leukemia Patients

Blood ◽  
1997 ◽  
Vol 90 (6) ◽  
pp. 2465-2470 ◽  
Author(s):  
J.F. San Miguel ◽  
A. Martı́nez ◽  
A. Macedo ◽  
M.B. Vidriales ◽  
C. López-Berges ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Multidrug Resistance ◽  
Minimal Residual Disease ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Leukemic Cells ◽  
Rhodamine 123 ◽  
Minimal Residual ◽  
Acute Myeloid

A high complete remission rate is currently achieved in patients with acute myeloid leukemia (AML). However, many patients eventually relapse due to the persistence of low numbers of residual leukemic cells that are undetectable by conventional cytomorphologic criteria (minimal residual disease [MRD]). Using immunophenotypic multiparametric flow cytometry, we have investigated in sequential studies (diagnosis and follow-up) the impact of MRD detection on the outcome of 53 AML patients that had achieved morphologic remission with standard AML protocols and displayed at diagnosis an aberrant phenotype. Patients were studied at diagnosis with a panel of 35 monoclonal antibodies in triple staining combinations for detection of aberrant or uncommon phenotypic features. According to these features, a patient's probe was custom-built at diagnosis for the identification of possible residual leukemic cells during follow-up. The level of MRD at the end of induction and intensification therapy correlated with the number of relapses and relapse-free survival (RFS). Thus, patients with more than 5 × 10−3 residual cells (5 residual cells among 1,000 normal bone marrow [BM] cells) identified as leukemic by immunophenotyping in the first remission BM showed a significant higher rate of relapse (67% v 20% for patients with less than 5 × 10−3 residual cells; P = .002) and a lower median RFS (17 months v not reached; P = .01). At the end of intensification, with a cut-off value of 2 × 10−3 leukemic cells, AML patients also separated into two distinct groups with relapse rates of 69% versus 32% (P = .02), respectively, and median RFS of 16 months versus not reached (P = .04). In addition, overall survival was also significantly related to the level of residual cells in the marrow obtained at the end of induction and particularly after intensification therapy (P = .008). Furthermore, we have explored whether residual disease was related with the functional expression of multidrug resistance (MDR-1) at diagnosis as assessed by the rhodamine-123 assay. Patients with ≥5 × 10−3 residual leukemic cells at the end of induction therapy had a significantly higher rhodamine-123 efflux (mean, 56% ± 24%) than those with less than 5 × 10−3 residual cells (mean, 32% ± 31%; P = .04). Finally, multivariate analysis showed that the number of residual cells at the end of induction or intensification therapy was the most important prognostic factor for prediction of RFS. Overall, our results show that immunophenotypical investigation of MRD strongly predicts outcome in patients with AML and that the number of residual leukemic cells correlates with multidrug resistance.

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