Effect of magnetic nanoparticles of Fe3O4 and 5-bromotetrandrine on reversal of multidrug resistance in K562/A02 leukemic cells

Cheng, Jian; Wu, Weiwei; Chen, Baoan; Gao, Feng; Xu, Wenlin; Gao, Chong; Ding, Jia-Hua; Sun, Yun-Yu; Song, Haoming; Wen, Bo; Sun, Xinchen; Xu, Cuirong; Chen, Wenji; Chen, Ning-Na; Liu, Lijie; Xia, Guohua; Li, Xiaomao; Wang, Xuemei

doi:10.2147/ijn.s7090

Cited by 28 publications

(27 citation statements)

References 15 publications

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“…It is exciting that magnetic nanoparticles, with their biodegradable nature, biocompatibility, and low toxicity, possess the capability to encapsulate a single drug or multiple drugs with a variety of properties, ranging from highly water-soluble to poorly water-soluble. [10][11][12][13] In addition, its passive targeting properties may reduce side effects during chemotherapy, 14 rendering it a promising drug delivery system. Therefore, in this study, to overcome the dose-limiting side effects of conventional chemotherapeutic agents, as well as to reduce the risk of therapeutic failure as a result of multidrug resistance, we undertook a rational design of biocompatible magnetic nanoparticles for sustained delivery of wogonin and daunorubicin and also investigated the potential mechanisms involved.…”

Section: Introductionmentioning

confidence: 99%

Effect of magnetic nanoparticles of Fe3O4 and wogonin on the reversal of multidrug resistance in K562/A02 cell line

Chen¹

2012

IJN

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Background: Multidrug resistance is the main obstacle to the efficiency of systemic chemotherapy against hematologic malignancy. This study investigated the reversible effect of the copolymer wogonin and daunorubicin coloaded into Fe 3 O 4 magnetic nanoparticles, and the mechanism potentially involved. Methods: The growth inhibition rate of K562/A02 cells was investigated by MTT assay, and apoptosis of cells and the intracellular daunorubicin concentration were detected by flow cytometry. Distribution of nanoparticles taken up by K562/A02 cells was observed under a transmission electron microscope and demonstrated by Prussian blue staining. The transcription level of MDR1 mRNA and expression of P-glycoprotein were determined by reverse transcriptase polymerase chain reaction and Western blotting assay, respectively. Results: The reversible effect of daunorubicin-wogonin magnetic nanoparticles was 8.87-fold that of daunorubicin + wogonin and of daunorubicin magnetic nanoparticles. Transmission electron microscopy and Prussian blue staining revealed that the nanoparticles were located in the endosome vesicles of cytoplasm. Also, the apoptosis rate and accumulation of intracellular daunorubicin in the daunorubicin-wogonin magnetic nanoparticle group were significantly higher than that in the daunorubicin, daunorubicin + wogonin, and daunorubicin magnetic nanoparticle groups. Furthermore, transcription of MDR1 mRNA and expression of P-glycoprotein in K562/ A02 cells were significantly downregulated in the daunorubicin-wogonin magnetic nanoparticle group compared with the other groups. Conclusion: These findings suggest that the remarkable effects of the novel daunorubicinwogonin magnetic nanoparticle formulation on multidrug resistant K562/A02 leukemia cells would be a promising strategy for overcoming multidrug resistance.

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Section: Introductionmentioning

confidence: 99%

Effect of magnetic nanoparticles of Fe3O4 and wogonin on the reversal of multidrug resistance in K562/A02 cell line

Chen¹

2012

IJN

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“…Moreover, iron oxide NPs may have additional utility as a contrast agent in magnetic resonance imaging or as a carrier for drug delivery. [11][12][13][14][15] In the present study, we focused on MgNPs-Fe 3 O 4 because of their potential to treat CRPC. This stems from the intrinsic properties of the magnetic core combined with the drug loading capability and the biomedical properties of MgNPs conferred by different surface coatings.…”

Section: Discussionmentioning

confidence: 99%

“…11 The combination of MgNPs with anticancer agents has been applied to leukemia, lung, and pancreatic cancer cells in vitro and to xenograft-injected nude mice. [12][13][14][15] MgNPs composed of Fe 3 O 4 (MgNPs-Fe 3 O 4 ) are being widely investigated for use as targeted drug carriers. The aim of this study was to evaluate the effect of treatment with MgNPsFe 3 O 4 or MgNPs-Fe 3 O 4 combined with DTX on prostate cancer cell growth in vitro.…”

Section: Introductionmentioning

confidence: 99%

Magnetic nanoparticles of Fe3O4 enhance docetaxel-induced prostate cancer cell death

Satô¹,

Itcho²,

Ishiguro³

et al. 2013

IJN

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Docetaxel (DTX) is one of the most important anticancer drugs; however, the severity of its adverse effects detracts from its practical use in the clinic. Magnetic nanoparticles of Fe 3 O 4 (MgNPs-Fe 3 O 4 ) can enhance the delivery and efficacy of anticancer drugs. We investigated the effects of MgNPs-Fe 3 O 4 or DTX alone, and in combination with prostate cancer cell growth in vitro, as well as with the mechanism underlying the cytotoxic effects. MgNPs-Fe 3 O 4 caused dose-dependent increases in reactive oxygen species levels in DU145, PC-3, and LNCaP cells; 8-hydroxydeoxyguanosine levels were also elevated. MgNPs-Fe 3 O 4 alone reduced the viability of LNCaP and PC-3 cells; however, MgNPs-Fe 3 O 4 enhanced the cytotoxic effect of a low dose of DTX in all three cell lines. MgNPs-Fe 3 O 4 also augmented the percentage of DU145 cells undergoing apoptosis following treatment with low dose DTX. Expression of nuclear transcription factor κB in DU145 was not affected by MgNPs-Fe 3 O 4 or DTX alone; however, combined treatment suppressed nuclear transcription factor κB expression. These findings offer the possibility that MgNPs-Fe 3 O 4 -low dose DTX combination therapy may be effective in treating prostate cancer with limited adverse effects.

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“…7 Briefly, total protein was isolated from the harvested cells in 25 mM Tris-HCl (pH = 7.4), 150 mM NaCl, 1% Triton X-100, 5 mM EDTA, 5 mM EGTA, 10 mM NaF, 1 mM PMSF, 0.5% NP-40, 10 µg/mL aprotinin, 10 µg/mL leupeptin, and 1 mM pepstatin for 15 minutes at 4°C and then centrifuged at 10,000 rpm for 5 minutes. …”

Section: Western Blotting Assaymentioning

confidence: 99%

Apoptotic mechanism of human leukemia K562/A02 cells induced by magnetic iron oxide nanoparticles co-loaded with daunorubicin and 5-bromotetrandrin

Wang

Chen²,

Cheng³

et al. 2011

IJN

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The purpose of this study was to assess the induced apoptosis of self-assembled iron oxide magnetic nanoparticles (MNPs) co-loaded with daunorubicin (DNR) and 5-bromotetrandrin (Br Tet) (DNR/Br Tet-MNPs), acting as a drug depot system for the sustained release of the loaded DNR and BrTet, in the drug resistant human leukemia K562/A02 cells and further to explore potential mechanisms. After being incubated for 48 hours, K562/A02 cells were treated with DNR/Br Tet-MNPs or DNR and Br Tet in solution (DNR/Br Tet-Sol). Morphologic characteristics of K562/A02 cells were observed under a fluorescence microscope; cell apoptosis and intracellular accumulation of DNR were analyzed by FACS Calibur flow cytometry. Furthermore, reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting analyses were performed to study the apoptosis associated gene transcription and protein expression, respectively. Typical apoptotic characteristics, including chromatin condensation and fragmentation of nuclei, were observed and a high rate of apoptosis was detected in K562/A02 cells treated with DNR/Br Tet-MNPs and DNR/Br Tet-Sol. Detection of relative fluorescence intensity of intracellular DNR demonstrated that intracellular DNR was higher in K562/A02 cells treated with DNR/Br Tet-MNPs than that of DNR/Br Tet-Sol. Further study demonstrated that both DNR/Br Tet-MNPs and DNR/Br Tet-Sol reduced the gene transcriptions and protein expressions of bcl-2 and survivin and enhanced that of bax and caspase 3 . It is concluded that self-assembled DNR/Br Tet-MNPs, as one of the potential antitumor agents for hematologic malignancies, may effectively induce apoptosis of K562/A02 cells through elevating the ratio of bax / bcl-2 , activating caspase 3 , and inactivating survivin .

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Effect of magnetic nanoparticles of Fe3O4 and 5-bromotetrandrine on reversal of multidrug resistance in K562/A02 leukemic cells

Cited by 28 publications

References 15 publications

Effect of magnetic nanoparticles of Fe3O4 and wogonin on the reversal of multidrug resistance in K562/A02 cell line

Effect of magnetic nanoparticles of Fe3O4 and wogonin on the reversal of multidrug resistance in K562/A02 cell line

Magnetic nanoparticles of Fe3O4 enhance docetaxel-induced prostate cancer cell death

Apoptotic mechanism of human leukemia K562/A02 cells induced by magnetic iron oxide nanoparticles co-loaded with daunorubicin and 5-bromotetrandrin

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