Apoptotic mechanism of human leukemia K562/A02 cells induced by magnetic iron oxide nanoparticles co-loaded with daunorubicin and 5-bromotetrandrin
Jun Wang¹, Baoan Chen¹, Jian Cheng¹, Xiaohui Cai¹, Guohua Xia¹, Ran Liu¹, Xuemei Wang²¹Department of Hematology, Zhongda Hospital, Medicine College; ²State Key Laboratory of Bioelectr...
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Dove Medical Press
2011
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oai:doaj.org-article:b0bc85221be242c49ea4868051b422fb2021-12-02T07:11:22ZApoptotic mechanism of human leukemia K562/A02 cells induced by magnetic iron oxide nanoparticles co-loaded with daunorubicin and 5-bromotetrandrin1176-91141178-2013https://doaj.org/article/b0bc85221be242c49ea4868051b422fb2011-05-01T00:00:00Zhttp://www.dovepress.com/apoptotic-mechanism-of-human-leukemia-k562a02-cells-induced-by-magneti-a7476https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Jun Wang¹, Baoan Chen¹, Jian Cheng¹, Xiaohui Cai¹, Guohua Xia¹, Ran Liu¹, Xuemei Wang²¹Department of Hematology, Zhongda Hospital, Medicine College; ²State Key Laboratory of Bioelectronics (Chien-Shiung Wu Laboratory), Southeast University, Nanjing, People's Republic of ChinaAbstract: 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.Keywords: magnetic iron oxide nanoparticles, daunorubicin, 5-bromotetrandrin, target therapy, multidrug resistance, apoptosis, K562/A02 cellsWang JChen BCheng JCai XXia GLiu RWang XDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2011, Iss default, Pp 1027-1034 (2011) |
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Medicine (General) R5-920 |
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Medicine (General) R5-920 Wang J Chen B Cheng J Cai X Xia G Liu R Wang X Apoptotic mechanism of human leukemia K562/A02 cells induced by magnetic iron oxide nanoparticles co-loaded with daunorubicin and 5-bromotetrandrin |
| description |
Jun Wang¹, Baoan Chen¹, Jian Cheng¹, Xiaohui Cai¹, Guohua Xia¹, Ran Liu¹, Xuemei Wang²¹Department of Hematology, Zhongda Hospital, Medicine College; ²State Key Laboratory of Bioelectronics (Chien-Shiung Wu Laboratory), Southeast University, Nanjing, People's Republic of ChinaAbstract: 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.Keywords: magnetic iron oxide nanoparticles, daunorubicin, 5-bromotetrandrin, target therapy, multidrug resistance, apoptosis, K562/A02 cells |
| format |
article |
| author |
Wang J Chen B Cheng J Cai X Xia G Liu R Wang X |
| author_facet |
Wang J Chen B Cheng J Cai X Xia G Liu R Wang X |
| author_sort |
Wang J |
| title |
Apoptotic mechanism of human leukemia K562/A02 cells induced by magnetic iron oxide nanoparticles co-loaded with daunorubicin and 5-bromotetrandrin |
| title_short |
Apoptotic mechanism of human leukemia K562/A02 cells induced by magnetic iron oxide nanoparticles co-loaded with daunorubicin and 5-bromotetrandrin |
| title_full |
Apoptotic mechanism of human leukemia K562/A02 cells induced by magnetic iron oxide nanoparticles co-loaded with daunorubicin and 5-bromotetrandrin |
| title_fullStr |
Apoptotic mechanism of human leukemia K562/A02 cells induced by magnetic iron oxide nanoparticles co-loaded with daunorubicin and 5-bromotetrandrin |
| title_full_unstemmed |
Apoptotic mechanism of human leukemia K562/A02 cells induced by magnetic iron oxide nanoparticles co-loaded with daunorubicin and 5-bromotetrandrin |
| title_sort |
apoptotic mechanism of human leukemia k562/a02 cells induced by magnetic iron oxide nanoparticles co-loaded with daunorubicin and 5-bromotetrandrin |
| publisher |
Dove Medical Press |
| publishDate |
2011 |
| url |
https://doaj.org/article/b0bc85221be242c49ea4868051b422fb |
| work_keys_str_mv |
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