title: Apoptotic mechanism of human leukemia K562/A02 cells induced by magnetic iron oxide nanoparticles co-loaded with daunorubicin and 5-bromotetrandrin.
abstract: 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.
authors: Department of Hematology, Zhongda Hospital, Medicine College, People's Republic of China.
authors: Jun
authors: J
authors: Wang
authors: Baoan
authors: B
authors: Chen
authors: Jian
authors: J
authors: Cheng
authors: Xiaohui
authors: X
authors: Cai
authors: Guohua
authors: G
authors: Xia
authors: Ran
authors: R
authors: Liu
authors: Xuemei
authors: X
authors: Wang
mesh_terms: D000704:Analysis of Variance; D017209:Apoptosis / Q000187:drug effects*; D044182:Benzylisoquinolines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003630:Daunorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems / Q000379:methods; D004587:Electrophoresis, Agar Gel; D005434:Flow Cytometry; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D044182:Benzylisoquinolines; D003692:Delayed-Action Preparations; D058185:Magnetite Nanoparticles; C514835:bromotetrandrine; D003630:Daunorubicin