Inhibitory effect of magnetic Fe₃O₄ nanoparticles coloaded with homoharringtonine on human leukemia cells in vivo and in vitro

Abstract

Homoharringtonine (HHT), a natural cephalotaxine alkaloid, has been used in the People’s Republic of China for treatment of leukemia for >3 decades. Here, we employed magnetic Fe 3 O 4 nanoparticles (MNP-Fe 3 O 4 ) to improve the therapeutic effect of HHT and investigated its biological effects. Within a certain range of concentrations, the HHT-MNP-Fe 3 O 4 showed a more enhanced inhibitory effect on the selected myeloid leukemia cell lines than HHT alone. Compared with HHT, HHT-MNP-Fe 3 O 4 could induce more extensive apoptosis in leukemia cells, which also showed more pronounced cell arrests at G0/G1 phase. HHT-MNP-Fe 3 O 4 enhanced antitumor activity by downregulating myeloid cell leukemia-1, which could inhibit the activation of caspase-3 and poly-ADP-ribose polymerase. In vivo experiments using tumor-bearing animal models showed that the mean tumor volume with HHT-MNP-Fe 3 O 4 was significantly smaller than that with HHT alone (193±26 mm 3 versus 457±100 mm 3 , P <0.05), while the mean weight was 0.67±0.03 g versus 1.42±0.56 g ( P <0.05). Immunohistochemical study showed fewer myeloid cell leukemia-1-stained cells in mice treated with HHT-MNP-Fe 3 O 4 than with the controls. These findings provide a more efficient delivery system for HHT in the treatment of hematological malignancy.

Homoharringtonine inhibits the progression of hepatocellular carcinoma by suppressing the PI3K/AKT/GSK3β/Slug signaling pathway

“…Moreover, the scientific community in Western countries has also identified the underlying plants linked to these natural products, especially the latent natural products of medicinal plants used in traditional Chinese medicine (TCM) [18]. Homoharringtonine (HHT) was first extracted from Cephalotaxus harringtonia (Knight ex J. Forbes) K. Koch and Cephalotaxus fortunei Hook [19] and has been used clinically to treat leukemia [20]. In recent years, HHT has also been used in research on various solid tumors, such as bladder, kidney, lung, and colorectal cancer [21][22][23][24].…”

Molecular Imaging of Matrix Metalloproteinase-2 in Atherosclerosis Using a Smart Multifunctional PET/MRI Nanoparticle

“…Firstly, magnetic Fe 3 O 4 nanoparticles were first prepared by reference. 24 10 mg Fe 3 O 4 dispersed in 5 mL chloroform and 20 mg dopamine dissolved in 3 mL dimethyl sulfoxide were added into a flash bottle successively. The reaction mixture was vigorously stirred to form a homogeneous solution and was heated at 70°C for 2 h before being cooled down to room temperature.…”

Recent advances and future prospects of iron oxide nanoparticles in biomedicine and diagnostics

“…They found cell death was caused due to apoptosis and observed cell cycle arrest at G0/G1 phase. Moreover, in vivo studies explained the combination worked efficiently to decrease the tumor volume compared to drug alone (Chen et al 2016 ). A similar study explained the combination of Fe 3 O 4 with adriamycin or daunorubicin drugs showed a potential inhibitory effect on lymphoma.…”

“…Results showed this drug loaded NPs can be efficiently delivered into blood brain barrier and can act as promising drug to treat blood tumors Xuhua Mao ( 2016 ) Homoharringtonine conjugated Fe 3 O 4 NPs 11.2 Used for in vitro and in vivo chemotherapy towards hematological malignancy. Results indicated drug conjugated MNPs injected in tumor bearing mice (leukemia) showed a significant decrease in tumor growth compared to drug treatment alone Chen et al ( 2016 ) Liposome with paclitaxel and SPIONs 159–168 Comprising both MRI and antitumor characteristics. Results showed the tumor growth was supressed in MDA-MB-231 tumor-bearing mice compared to controls Zheng et al ( 2018 ) Fe 3 O 4 NPs with adriamycin and daunorubicin – Used as a combination therapy to treat lymphoma.…”