Inducing cell cycle arrest and apoptosis by dimercaptosuccinic acid modified Fe3O4 magnetic nanoparticles combined with nontoxic concentration of bortezomib and gambogic acid in RPMI-8226 cells
Wei Zhang,1* Lixing Qiao,2* Xinchao Wang,3* Ravichandran Senthilkumar,1 Fei Wang,1 Baoan Chen1,4 1Medical School, Southeast University, Nanjing, People’s Republic of China; 2Department of Pediatrics, Zhongda Hospital, Medical School, Southeast University, Nanjing, People’s Repub...
Guardado en:
| Autores principales: | , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Dove Medical Press
2015
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/db6caba790c14dd4b4511c91513a6a61 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:db6caba790c14dd4b4511c91513a6a61 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:db6caba790c14dd4b4511c91513a6a612021-12-02T02:10:26ZInducing cell cycle arrest and apoptosis by dimercaptosuccinic acid modified Fe3O4 magnetic nanoparticles combined with nontoxic concentration of bortezomib and gambogic acid in RPMI-8226 cells1178-2013https://doaj.org/article/db6caba790c14dd4b4511c91513a6a612015-04-01T00:00:00Zhttp://www.dovepress.com/inducing-cell-cycle-arrest-and-apoptosis-bynbspdimercaptosuccinic-acid-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Wei Zhang,1* Lixing Qiao,2* Xinchao Wang,3* Ravichandran Senthilkumar,1 Fei Wang,1 Baoan Chen1,4 1Medical School, Southeast University, Nanjing, People’s Republic of China; 2Department of Pediatrics, Zhongda Hospital, Medical School, Southeast University, Nanjing, People’s Republic of China; 3Department of Thyroid and Breast, the Fourth Central Hospital, Tianjin, People’s Republic of China; 4Department of Hematology and Oncology, Zhongda Hospital, Medical School, Southeast University, Nanjing, People’s Republic of China *These authors contributed equally to this work Abstract: The purpose of this study was to determine the potential benefits of combination therapy using dimercaptosuccinic acid modified iron oxide (DMSA-Fe3O4) magnetic nanoparticles (MNPs) combined with nontoxic concentration of bortezomib (BTZ) and gambogic acid (GA) on multiple myeloma (MM) RPMI-8226 cells and possible underlying mechanisms. The effects of BTZ-GA-loaded MNP-Fe3O4 (BTZ-GA/MNPs) on cell proliferation were assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,4,-diphenyltetrazolium bromide (MTT) method. Cell cycle and apoptosis were detected using the terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling (TUNEL) assay and flow cytometry (FCM). Furthermore, DMSA-Fe3O4 MNPs were characterized in terms of distribution, apoptotic morphology, and cellular uptake by transmission electron microscopy (TEM) and 4,6-diamidino-2-phenylindole (DAPI) staining. Subsequently, the effect of BTZ-GA/MNPs combination on PI3K/Akt activation and apoptotic-related protein were appraised by Western blotting. MTT assay and hematoxylin and eosin (HE) staining were applied to elevate the functions of BTZ-GA/MNPs combination on the tumor xenograft model and tumor necrosis. The results of this study revealed that the majority of MNPs were quasi-spherical and the MNPs taken up by cells were located in the endosome vesicles of cytoplasm. Nontoxic concentration of BTZ-GA/MNPs increased G2/M phase cell cycle arrest and induced apoptosis in RPMI-8226 cells. Furthermore, the combination of BTZ-GA/MNPs activated phosphorylated Akt levels, Caspase-3, and Bax expression, and down-regulated the PI3K and Bcl-2 levels significantly. Meanwhile, the in vivo tumor xenograft model indicated that the treatment of BTZ-GA/MNPs decreased the tumor growth and volume and induced cell apoptosis and necrosis. These findings suggest that chemotherapeutic agents polymerized MNPs-Fe3O4 with GA could serve as a better alternative for targeted therapeutic approaches to treat multiple myeloma. Keywords: magnetic nanoparticles, DMSA-Fe3O4, bortezomib, gambogic acid, PI3K/Akt, cell cycle, apoptosisZhang WQiao LWang XSenthilkumar RWang FChen BDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 3275-3289 (2015) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine (General) R5-920 |
| spellingShingle |
Medicine (General) R5-920 Zhang W Qiao L Wang X Senthilkumar R Wang F Chen B Inducing cell cycle arrest and apoptosis by dimercaptosuccinic acid modified Fe3O4 magnetic nanoparticles combined with nontoxic concentration of bortezomib and gambogic acid in RPMI-8226 cells |
| description |
Wei Zhang,1* Lixing Qiao,2* Xinchao Wang,3* Ravichandran Senthilkumar,1 Fei Wang,1 Baoan Chen1,4 1Medical School, Southeast University, Nanjing, People’s Republic of China; 2Department of Pediatrics, Zhongda Hospital, Medical School, Southeast University, Nanjing, People’s Republic of China; 3Department of Thyroid and Breast, the Fourth Central Hospital, Tianjin, People’s Republic of China; 4Department of Hematology and Oncology, Zhongda Hospital, Medical School, Southeast University, Nanjing, People’s Republic of China *These authors contributed equally to this work Abstract: The purpose of this study was to determine the potential benefits of combination therapy using dimercaptosuccinic acid modified iron oxide (DMSA-Fe3O4) magnetic nanoparticles (MNPs) combined with nontoxic concentration of bortezomib (BTZ) and gambogic acid (GA) on multiple myeloma (MM) RPMI-8226 cells and possible underlying mechanisms. The effects of BTZ-GA-loaded MNP-Fe3O4 (BTZ-GA/MNPs) on cell proliferation were assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,4,-diphenyltetrazolium bromide (MTT) method. Cell cycle and apoptosis were detected using the terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling (TUNEL) assay and flow cytometry (FCM). Furthermore, DMSA-Fe3O4 MNPs were characterized in terms of distribution, apoptotic morphology, and cellular uptake by transmission electron microscopy (TEM) and 4,6-diamidino-2-phenylindole (DAPI) staining. Subsequently, the effect of BTZ-GA/MNPs combination on PI3K/Akt activation and apoptotic-related protein were appraised by Western blotting. MTT assay and hematoxylin and eosin (HE) staining were applied to elevate the functions of BTZ-GA/MNPs combination on the tumor xenograft model and tumor necrosis. The results of this study revealed that the majority of MNPs were quasi-spherical and the MNPs taken up by cells were located in the endosome vesicles of cytoplasm. Nontoxic concentration of BTZ-GA/MNPs increased G2/M phase cell cycle arrest and induced apoptosis in RPMI-8226 cells. Furthermore, the combination of BTZ-GA/MNPs activated phosphorylated Akt levels, Caspase-3, and Bax expression, and down-regulated the PI3K and Bcl-2 levels significantly. Meanwhile, the in vivo tumor xenograft model indicated that the treatment of BTZ-GA/MNPs decreased the tumor growth and volume and induced cell apoptosis and necrosis. These findings suggest that chemotherapeutic agents polymerized MNPs-Fe3O4 with GA could serve as a better alternative for targeted therapeutic approaches to treat multiple myeloma. Keywords: magnetic nanoparticles, DMSA-Fe3O4, bortezomib, gambogic acid, PI3K/Akt, cell cycle, apoptosis |
| format |
article |
| author |
Zhang W Qiao L Wang X Senthilkumar R Wang F Chen B |
| author_facet |
Zhang W Qiao L Wang X Senthilkumar R Wang F Chen B |
| author_sort |
Zhang W |
| title |
Inducing cell cycle arrest and apoptosis by dimercaptosuccinic acid modified Fe3O4 magnetic nanoparticles combined with nontoxic concentration of bortezomib and gambogic acid in RPMI-8226 cells |
| title_short |
Inducing cell cycle arrest and apoptosis by dimercaptosuccinic acid modified Fe3O4 magnetic nanoparticles combined with nontoxic concentration of bortezomib and gambogic acid in RPMI-8226 cells |
| title_full |
Inducing cell cycle arrest and apoptosis by dimercaptosuccinic acid modified Fe3O4 magnetic nanoparticles combined with nontoxic concentration of bortezomib and gambogic acid in RPMI-8226 cells |
| title_fullStr |
Inducing cell cycle arrest and apoptosis by dimercaptosuccinic acid modified Fe3O4 magnetic nanoparticles combined with nontoxic concentration of bortezomib and gambogic acid in RPMI-8226 cells |
| title_full_unstemmed |
Inducing cell cycle arrest and apoptosis by dimercaptosuccinic acid modified Fe3O4 magnetic nanoparticles combined with nontoxic concentration of bortezomib and gambogic acid in RPMI-8226 cells |
| title_sort |
inducing cell cycle arrest and apoptosis by dimercaptosuccinic acid modified fe3o4 magnetic nanoparticles combined with nontoxic concentration of bortezomib and gambogic acid in rpmi-8226 cells |
| publisher |
Dove Medical Press |
| publishDate |
2015 |
| url |
https://doaj.org/article/db6caba790c14dd4b4511c91513a6a61 |
| work_keys_str_mv |
AT zhangw inducingcellcyclearrestandapoptosisbynbspdimercaptosuccinicacidmodifiedfe3o4magneticnanoparticlescombinedwithnontoxicconcentrationofbortezomibandgambogicacidnbspinrpmi8226cells AT qiaol inducingcellcyclearrestandapoptosisbynbspdimercaptosuccinicacidmodifiedfe3o4magneticnanoparticlescombinedwithnontoxicconcentrationofbortezomibandgambogicacidnbspinrpmi8226cells AT wangx inducingcellcyclearrestandapoptosisbynbspdimercaptosuccinicacidmodifiedfe3o4magneticnanoparticlescombinedwithnontoxicconcentrationofbortezomibandgambogicacidnbspinrpmi8226cells AT senthilkumarr inducingcellcyclearrestandapoptosisbynbspdimercaptosuccinicacidmodifiedfe3o4magneticnanoparticlescombinedwithnontoxicconcentrationofbortezomibandgambogicacidnbspinrpmi8226cells AT wangf inducingcellcyclearrestandapoptosisbynbspdimercaptosuccinicacidmodifiedfe3o4magneticnanoparticlescombinedwithnontoxicconcentrationofbortezomibandgambogicacidnbspinrpmi8226cells AT chenb inducingcellcyclearrestandapoptosisbynbspdimercaptosuccinicacidmodifiedfe3o4magneticnanoparticlescombinedwithnontoxicconcentrationofbortezomibandgambogicacidnbspinrpmi8226cells |
| _version_ |
1718402680949309440 |