Apoptotic Mechanism of Human Leukemia K562/A02 Cells Induced by Magnetic Ferroferric Oxide Nanoparticles Loaded with Wogonin

BACKGROUND: Traditional Chinese medicine wogonin plays an important role in the treatment of leukemia. Recently, the application of drug-coated magnetic nanoparticles (MNPs) to increase water solubility of the drug and to enhance its chemotherapeutic efficiency has attracted much attention. Drugs coated with MNPs are becoming a promising way for better leukemia treatment. This study aimed to assess the possible molecular mechanisms of wogonin-coated MNP-Fe(3)O(4) (Wog-MNPs-Fe(3)O(4)) as an antileukemia agent. METHODS: After incubated for 48 h, the antiproliferative effects of MNPs, wogonin, or Wog-MNPs-Fe(3)O(4) on K562/A02 cells were determined by methyl thiazolyl tetrazolium (MTT) assay. The apoptotic rates of K562/A02 cells treated with either wogonin or Wog-MNPs-Fe(3)O(4) were determined by flow cytometer (FCM) assay. The cell cycle arrest in K562/A02 cells was determined by FCM assay. The elementary molecular mechanisms of these phenomena were explored by Western blot and reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: With cell viabilities ranging from 98.76% to 101.43%, MNP-Fe(3)O(4) was nontoxic to the cell line. Meanwhile, the wogonin and Wog-MNPs-Fe(3)O(4) had little effects on normal human embryonic lung fibroblast cells. The cell viabilities of the Wog-MNPs-Fe(3)O(4) group (28.64–68.36%) were significantly lower than those of the wogonin group (35.53–97.28%) in a dose-dependent manner in 48 h (P < 0.001). The apoptotic rate of K562/A02 cells was significantly improved in 50 μmol/L Wog-MNPs-Fe(3)O(4) group (34.28%) compared with that in 50 μmol/L wogonin group (23.46%; P < 0.001). Compared with those of the 25 and 50 μmol/L wogonin groups, the ratios of G0/G1-phase K562/A02 cells were significantly higher in the 25 and 50 μmol/L Wog-MNPs-Fe(3)O(4) groups (all P < 0.001). The mRNA and protein expression levels of the p21 and p27 in the K562/A02 cells were also significantly higher in the Wog-MNPs-Fe(3)O(4) group compared with those of the wogonin group (all P < 0.001). CONCLUSIONS: This study demonstrated that MNPs were the effective drug delivery vehicles to deliver wogonin to the leukemia cells. Through increasing cells arrested at G0/G1-phase and inducing apoptosis of K562/A02 cells, MNPs could enhance the therapeutic effects of wogonin on leukemia cells. These findings indicated that MNPs loaded with wogonin could provide a promising way for better leukemia treatment.