Invivo and invitro evaluation of antitumor effects of iron oxide and folate core shell-iron oxide nanoparticles

2024 ◽  
Vol 84 ◽  
Author(s):  
N. N. H. Shosha ◽  
S. Elmasry ◽  
M. Moawad ◽  
S. H. Ismail ◽  
M. Elsayed
Keyword(s):  
Iron Oxide ◽  
Cell Cultures ◽  
Caspase 3 ◽  
Complete Blood Count ◽  
Oral Treatment ◽  
Core Shell ◽  
Acute Myelocytic Leukemia ◽  
Human Leukemia ◽  
Mrna Levels ◽  
Antitumor Effects

Abstract Nanoparticles are considered viable options in the treatment of cancer. This study was conducted to investigate the effect of magnetite nanoparticles (MNPs) and magnetite folate core shell (MFCS) on leukemic and hepatocarcinoma cell cultures as well as their effect on the animal model of acute myelocytic leukemia (AML). Through current study nanoparticles were synthesized, characterized by various techniques, and their properties were studied to confirm their nanostructure. Invivo study, nanoparticles were evaluated to inspect their cytotoxic activity against SNU-182 (human hepatocellular carcinoma), K562 (human leukemia), and THLE2 (human normal epithelial liver) cells via MTT test. Apoptotic signaling proteins Bcl-2 and Caspase-3 expression were inspected through RT-PCR method. A cytotoxic effect of MNPs and MFCS was detected in previous cell cultures. Moreover, the apoptosis was identified through significant up-regulation of caspase-3, with Bcl-2 down-regulation. Invitro study, AML was induced in rats by N-methyl-N-nitrosourea followed by oral treatment with MNPS and MFCS. Biochemical indices such as aspartate and alanine amino transferases, and lactate dehydrogenase activities, uric acid, complete blood count, and Beta -2-microglubulin were assessed in serum. Immunophenotyping for CD34 and CD38 detection was performed. Liver, kidney, and bone marrow were microscopically examined. Bcl-2 promoter methylation, and mRNA levels were examined. Although, both MNPs and MFCS depict amelioration in biochemical parameters, MFCS alleviated them toward normal control. Anticancer activity of MNPs and MFCS was approved especially for AML. Whenever, administration of MFCS was more effective than MNPs. The present work is one of few studies used MFCS as anticancer agent.

scholarly journals The Effect of Kynurenic Acid on Apoptosis in Hepatocellular Carcinoma

Proceedings ◽  
2019 ◽  
Vol 40 (1) ◽  
pp. 6
Author(s):  
Atalay ◽  
Imamoglu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Glutamate Receptors ◽  
Hepg2 Cells ◽  
Kynurenic Acid ◽  
Caspase 3 ◽  
Mrna Levels ◽  
Antitumor Effects ◽  
Glutamate Antagonists ◽  
Effector Caspase

Kynurenic Acid (KYNA) is a metabolite of tryptophan pathway and also an endogenous antagonist of glutamate receptors. Several studies indicated that glutamate antagonists have anti-proliferative potential. Moreover, subunits of the NMDA receptor which is one of the glutamate receptors have been shown to be found in human hepatocellular carcinoma cell line (HepG2). In this study, the antitumor effects of KYNA in HepG2 cells were investigated for the first time at the molecular level. The effects of KYNA on the viability of HepG2 cells were determined by MTT analyses. Effects of KYNA on mRNA transcriptions of apoptosis related genes Bax, Bcl-2 and Caspase-3 were analyzed by qRT-PCR. mRNA expression analysis revealed that the mRNA levels of effector Caspase-3 and pro-apoptotic Bax/Bcl-2 ratio were not increased in HepG2 cells treated with KYNA. In conclusion, our findings showed that KYNA does not exert its anti-proliferative effects on HepG2 cells through caspase-mediated apoptotic cell death, but it may perform this anti-proliferative effect through a different mechanism of death. Further studies are needed to find out potential cell death mechanisms that may play a role in anti-proliferative activity of KYNA on HepG2 cells.

scholarly journals Synthesis of Superparamagnetic Iron Oxide Nanoparticle (SPIONs) for Drug Delivery and X-ray Imaging

2020 ◽  
Vol 2 (1) ◽  
pp. 3
Keyword(s):  
Drug Delivery ◽  
Iron Oxide ◽  
Caspase 3 ◽  
Superparamagnetic Iron Oxide ◽  
Core Shell ◽  
Nuclear Staining ◽  
X Ray ◽  
The Core ◽  
X Ray Imaging ◽  
Hct 116

Precursor iron molecular solution for the synthesis of SPIONs was optimized for the production of superparamagnetic iron oxide nanoparticles (SPIONs). Thus produced SPIONs were subjected for core-shell – SPIONs synthesis for drug delivery, which had the following four major stages (1) synthesis of SPIONs, (2) functionalization of SPIONs, (3) curcumin loading, and (4) biopolymer coating (Chitosan). Every stage of the synthesis was analyzed using various microscopic (TEM, SEM, AFM) and spectroscopic (UV Vis, FTIR, Zeta Analyzer, Raman Spectroscopy, GIXRD, PXRD, XPS, SQUID, VSM) analysis. Through spectroscopic techniques, mainly the elemental nature and the energy states of elements present all through the core-shell production were studied. The core-shells were subjected to drug delivery studies against HCT 116 and HeLa cells. Core-shell SPIONs were showing IC50 at 30μg and 80μg concentration against HeLa and HCT 116 cell lines, respectively. IC50 concentration was subjected for further anticancer studies through nuclear staining, flow cytometry, and expression of caspase 3 at four-time duration: 2 hours, 6 hours, 12 hours, and 24 hours. The core-shell SPIONs were found to induce cancer apoptosis, which was analyzed using quadrant and histogram statistics obtained as per flow-cytometer. Caspase 3 expression was analyzed using a caspase expression assay. Further, they were evaluated by histogram statistics. SPIONs were utilized as a contrasting agent for X-ray imaging, where it was showing the egg visibility. The response of SPIONs to X-ray was studied with and without the applied magnetic field. Later, the SPIONs were subjected to toxicity study against earthworm.

The DNA methyl transferase inhibitor, 5′-aza-2-deoxycitidine, enhances the apoptotic effect of Mevastatin in human leukemia HL-60 cells

2013 ◽  
Vol 33 (4) ◽  
pp. 414-423 ◽  
Author(s):  
A Yilmaz ◽  
S Menevse ◽  
E Konac ◽  
E Alp
Keyword(s):  
Dna Synthesis ◽  
Mrna Expression ◽  
Dna Fragmentation ◽  
Caspase 3 ◽  
Synthesis Rate ◽  
Human Leukemia ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Apoptotic Response

Statins induce antiproliferative effects and apoptotic response in various cancer cell types. Moreover, they also sensitize tumor cell lines from different origins to many agents. We aimed to investigate possible effects of Mevastatin (Mev) alone and sequential treatment of 5′-aza-2-deoxycitidine (DAC) and Mev on HL-60 cell line using XTT (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) assay, lactate dehydrogenase release assay, flourescence microscopy, DNA fragmentation analysis, determination of DNA synthesis rate, and active caspase-3 assay. Messenger RNA (mRNA) expression of apoptotic and antiapoptotic genes were also evaluated by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) for BAX, BCL2, and XIAP genes and quantitative Real-time PCR for CASP3, CASP8, and CASP9 genes. We showed that treatment with Mev alone and DAC followed by Mev resulted in apoptotic response in a time- and dose-dependent manner. We also found that pretreatment with DAC sensitized HL-60 cells to Mev and caused more apoptotic cell death than Mev-alone treatment via caspase-3 activation and DNA fragmentation. Moreover, sequential addition of Mev after DAC diminished DNA synthesis rate more effectively than Mev-alone treatment. Furthermore, DAC pretreatment significantly increased CASP3 and CASP9 mRNA expression even with lower doses of Mev. BAX, BCL2, and XIAP gene mRNA levels were also found to be changed in the presence of DAC and Mev. Determination of the exact molecular effects of statins and DAC would allow us to identify new molecular targets to develop more effective treatment regimens for cancer.

Novel Microemulsion of Tanshinone IIA, Isolated from Salvia miltiorrhiza Bunge, Exerts Anticancer Activity Through Inducing Apoptosis in Hepatoma Cells

2013 ◽  
Vol 41 (01) ◽  
pp. 197-210 ◽  
Author(s):  
Hui Ma ◽  
Qing Fan ◽  
Jia Yu ◽  
Jile Xin ◽  
Ce Zhang
Keyword(s):  
Drug Delivery ◽  
Caspase 3 ◽  
Salvia Miltiorrhiza ◽  
Ethyl Oleate ◽  
Tanshinone Iia ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Antitumor Effects ◽  
Protein Levels ◽  
Dose Dependent

Natural product Tanshinone IIA (TanIIA) induces apoptosis and differentiation in hepatocellular carcinoma (HCC) cells, but its clinical use is limited due to poor water solubility and lack of appropriate formulations for drug delivery. In this study, we capsulated TanIIA into a microemulsion (ME) that was composed of phospholipid, ethyl oleate, glycerol and pluronic F68. We then determined the anticancer effects and mechanisms of action for TanIIA ME with in vitro and in vivo HCC models. The mRNA and protein levels of apoptosis-related molecules (Bcl-2, Bax and caspase-3) were analyzed in murine hepatoma H22 cells and H22 tumor-bearing mice by flow cytometry, RT-PCR and immunofluorescence staining. Compared with the groups treated with empty ME and drug solution, the mRNA levels of Bax and caspase-3 were up-regulated, and the mRNA and protein levels of Bcl-2 were down-regulated in H22 cells treated with TanIIA ME in a dose-dependent manner. The mRNA and protein levels of Bax and caspase-3 were up-regulated and the Bcl-2 levels were also down-regulated in animals treated with TanIIA ME in a dose-dependent manner. Our results suggest that as a novel drug delivery system, microemulsion enhances the antitumor effects of TanIIA.

scholarly journals Determining the size of nanoparticles in the example of magnetic iron oxide core-shell systems

2017 ◽  
Vol 885 ◽  
pp. 012007 ◽  
Author(s):  
Maciej Jarzębski ◽  
Mikołaj Kościński ◽  
Tomasz Białopiotrowicz
Keyword(s):  
Iron Oxide ◽  
Core Shell ◽  
Magnetic Iron Oxide ◽  
Iron Oxide Core

Iron Oxide-Gold Core-Shell Nanoparticles as Multimodal Imaging Contrast Agent

2013 ◽  
Vol 13 (6) ◽  
pp. 2341-2347 ◽  
Author(s):  
Luca Menichetti ◽  
Leonardo Manzoni ◽  
Luigi Paduano ◽  
A. Flori ◽  
Claudia Kusmic ◽  
...  
Keyword(s):  
Iron Oxide ◽  
Contrast Agent ◽  
Multimodal Imaging ◽  
Core Shell ◽  
Shell Nanoparticles ◽  
Gold Core ◽  
Core Shell Nanoparticles ◽  
Imaging Contrast Agent

Water Oxidation Catalysis by Birnessite@Iron Oxide Core–Shell Nanocomposites

2015 ◽  
Vol 54 (6) ◽  
pp. 2734-2741 ◽  
Author(s):  
Gökhan Elmaci ◽  
Carolin E. Frey ◽  
Philipp Kurz ◽  
Birgül Zümreoğlu-Karan
Keyword(s):  
Iron Oxide ◽  
Water Oxidation ◽  
Oxidation Catalysis ◽  
Core Shell ◽  
Water Oxidation Catalysis ◽  
Iron Oxide Core

Synthesis and biological activities of chaetocin and its derivatives

2012 ◽  
Vol 84 (6) ◽  
pp. 1369-1378 ◽  
Author(s):  
Mikiko Sodeoka ◽  
Kosuke Dodo ◽  
Yuou Teng ◽  
Katsuya Iuchi ◽  
Yoshitaka Hamashima ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Caspase 3 ◽  
Biological Activities ◽  
Caspase 8 ◽  
Human Leukemia ◽  
Mechanistic Studies ◽  
Anticancer Activities ◽  
Histone Methyltransferases ◽  
Structure Activity ◽  
Apoptosis Inducer

Chaetocin, a natural product isolated from fungi of Chaetomium species, is a member of the epipolythiodiketopiperazines (ETPs), which have various biological activities, including cytostatic and anticancer activities. Recently, the inhibitory activity toward histone methyltransferases (HMTs) was discovered for chaetocin. We previously reported the first total synthesis of chaetocin and various derivatives. During studies on the structure–activity relationship for HMT inhibition, we found that the enantiomer of chaetocin (ent-chaetocin) is a more potent apoptosis inducer than natural chaetocin in human leukemia HL-60 cells. Mechanistic studies showed that ent-chaetocin induces apoptosis through the caspase-8/caspase-3 pathway.

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