Human Hepatocellular Liver Carcinoma Cell Research Articles

High fluorescence of carbazole derivatives for bioimaging of endoplasmic reticulum and lysosome: the influence of molecular structure on optical properties and cell uptake

Three new carbazole derivatives (L1–L3) with different functional groups have been synthesized and characterized. L1 and L2 are connected through methylene unit to construct L3 with enhanced molecular distortion configuration. The compounds exhibit dependent aggregation-induced enhanced emission (AIEE) properties and cellar uptake region in HepG2 cells. It is demonstrated that L1 and L2 exhibit modest AIEE properties in THF–H2O mixtures, while L3 shows superior AIEE character with 13 times enhancement. This is because of the enhanced molecular distortion configuration of L3 and the related restriction of π–π stacking interactions between adjacent L3 molecules resulted from the introduction of methylene unit. Due to the unique structure of the compounds, the superior fluorescence emission of L1–L3 in aqueous media, further imaging studies demonstrated the suitability of probes L1–L3 for the biological applications in both human liver hepatocellular carcinoma cells (HepG2) and plant tissues of Arabidopsis seedlings. The imidazole unit in L2 leads selective target to lysosome of HepG2 cells through acid–base interactions, while L1 and L3 are inclined to act with endoplasmic reticulum.

Identification and risk assessment of human and veterinary antibiotics in the wastewater treatment plants and the adjacent sea in Tunisia.

In the following study, we came up with and validated a prompt, sensitive and precise method for the simultaneous determination of 56 antimicrobial drugs (tetracyclines, sulfonamides, β-lactams, macrolides and quinolones) using the ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). This method was implemented with success to determine antibiotics in samples collected from four wastewater treatment plants and five coasts in Tunisia. Results showed the presence of high concentrations of antibiotics that ranged from 0.1 to 646 ng mL-1, which can induce many negative impacts on health and the environment. For this reason, we have opted to evaluate toxicity of wastewater samples using a battery of biotests. In fact, genotoxicity was assessed using three tests: Vitotox, comet and micronucleus assays. The input and output of wastewater treatment plants induced a strongly genotoxic effect on the Salmonella typhimurium TA104 prokaryotic Vitotox assay. This result was confirmed using the comet and the micronucleus assays performed on the human liver hepatocellular carcinoma cells. The genotoxic power of the tested wastewater treatment plants' samples could be attributed to the presence of the higher quantities of antibiotics that are detected in these samples and to the antibiotic and organic compound cocktails.

Cetuximab-conjugated nanodiamonds drug delivery system for enhanced targeting therapy and 3D Raman imaging.

In this study, a multicomponent nanodiamonds (NDs)-based targeting drug delivery system, cetuximab-NDs-cisplatin bioconjugate, combining both specific targeting and enhanced therapeutic efficacy capabilities, is developed and characterized. The specific targeting ability of cetuximab-NDs-cisplatin system on human liver hepatocellular carcinoma (HepG2) cells is evaluated through epidermal growth factor receptor (EGFR) blocking experiments, since EGFR is over-expressed on HepG2 cell membrane. Besides, cytotoxic evaluation confirms that cetuximab-NDs-cisplatin system could significantly inhibit the growth of HepG2 cells, and the therapeutic activity of this system is proven to be better than that of both nonspecific NDs-cisplatin conjugate and specific EGF-NDs-cisplatin conjugate. Furthermore, a 3-dimensional (3D) Raman imaging technique is utilized to visualize the targeting efficacy and enhanced internalization of cetuximab-NDs-cisplatin system in HepG2 cells, using the NDs existing in the bioconjugate as Raman probes, based on the characteristic Raman signal of NDs at 1332 cm-1 . These advantageous properties of cetuximab-NDs-cisplatin system propose a prospective imaging and treatment tool for further diagnostic and therapeutic purposes.

Synthesis and Evaluation of Cytotoxic Activity of Some Pyrroles and Fused Pyrroles.

Pyrrole derivatives represent a very interesting class as biologically active compounds. The objective of our study was to investigate the cytotoxic and apoptotic effects and antioxidant activity of the newly synthesized pyrrole derivatives. A series of novel pyrroles and fused pyrroles (tetrahydroindoles, pyrrolopyrimidines, pyrrolopyridines and pyrrolotriazines) were synthesized and characterized using IR, 1H NMR, 13C NMR, MS and elemental analysis techniques. The antiproliferative activity of our synthesized compounds and their modulatory effect apoptotic pathway were investigated. The effect on cellular proliferation and viability was monitored by resazurin assay. Apoptotic effect was evaluated by caspase glo 3/7 assay. Synthesized compounds are then tested for their anticancer activities against three different cell lines representing three different tumor types, namely; the HepG-2 (Human hepatocellular liver carcinoma cell line), the human MCF-7 cell line (breast cancer) and the pancreatic resistant Panc-1 cells. Compounds Ia-e, IIe, and IXc, d showed a promising anti-cancer activity on all tested cell lines. Antioxidant and wound healing invasion assays were examined for promising anticancer candidate compounds.

Synthesis, Characterization, and Molecular Docking of Novel bis‐thiazolyl Thienothiophene Derivatives as Promising Cytotoxic Antitumor Drug

A novel, facile reaction for the synthesis of series of bis‐thiazole derivatives has been developed from the reaction of the appropriate thiosemicarbazone derivatives and bis‐2‐bromoacetylthieno[2,3‐b]thiophene derivatives in ethanol under reflux. The structures of the newly synthesized products were established on the basis of spectral data (mass, IR, and 1H and 13C NMR) and elemental analyses. Fifteen compounds of the synthesized compounds were evaluated for their anticancer activity against human liver hepatocellular carcinoma cell line (HepG2). All compounds showed anticancer activity but differs in potency comparable with the reference drug Cisplatin. Moreover, molecular docking study using MOE software predicted the best binding mode between the most active compound 5o into the active site of human heat‐shock protein 90. The computational studies are confirming the results in biological activity.

Design, synthesis and biological evaluation of novel hydroxamates and 2-aminobenzamides as potent histone deacetylase inhibitors and antitumor agents

Many studies have indicated that histone deacetylase (HDAC) inhibitors are promising agents for the treatment of cancer. With the aim to search for novel potent HDAC inhibitors, we designed and synthesized two series of hydroxamates and 2-aminobenzamides compounds as HDAC inhibitors and antitumor agents. Those compounds were investigated for their HDAC enzymatic inhibitory activities and in vitro anti-proliferation activities against diverse cancer cell line (A549, HepG2, MGC80-3 and HCT116). Most of the synthesized compounds displayed potent HDAC inhibitory activity and antiproliferative activity. In particular, Compound 12a, N-(2-aminophenyl)-4-[(4-fluorophenoxy)methyl]benzamide, was shown to have the most HDAC inhibitory activity (70.6% inhibition at 5 μM) and antitumor activity with IC50 value of as low as 3.84 μM against HepG2 human liver hepatocellular carcinoma cell line, more than 4.8–fold lower than CS055 and 5.9–fold lower than CI994. HDAC isoform selectivity assay indicated 12a is a potent HDAC2 inhibitor. Docking study of 12a suggested that it bound tightly to the binding pocket of HDAC2. Further investigation showed that 12a could inhibit the migration and colony formation of A549 cancer cells. Furthermore, 12a remarkably induced apoptosis and G2/M phase cell cycle arrest in A549 cancer cells. Those results indicated that compound 12a could be a promising candidate for treatment of cancer.

Cytotoxic potential of rhizome extracts of Hedychium spicatum L. in HepG2 cell line using MTT

The present study was designed to evaluate the cytotoxic effects of extract of Hedychium spicatum rhizome extract on human liver hepatocellular carcinoma (HepG2) cell line using MTT assay. The crude extract of H. spicatum was prepared by cold maceration method, filtered, concentrated in different organic solution and tested for phytochemical evaluation and finally on HepG2 cell line. Dose-dependent cytotoxic activities were exhibited on HepG2 cell line. As the dose of the extract increased, the number of viable cells decreased. This confirms the cytotoxic potential of the rhizome of H. spicatum. The IC50 value of different extracts was determined and concluded that the methanolic extract had better potential than the other extracts.

Synthesis and Evaluation of New Pyrazoline Derivatives as Potential Anticancer Agents in HepG-2 Cell Line.

Cancer is a major public health concern worldwide. Adverse effects of cancer treatments still compromise patients’ quality of life. To identify new potential anticancer agents, a series of novel pyrazoline derivatives were synthesized and evaluated for cytotoxic effects on HepG-2 (human liver hepatocellular carcinoma cell line) and primary hepatocytes. Compound structures were confirmed by 1H-NMR, mass spectrometry, and infrared imaging. An in vitro assay demonstrated that several compounds exerted cytotoxicity in the micromolar range. Benzo[b]thiophen-2-yl-[5-(4-hydroxy-3,5-dimethoxy-phenyl)-3-(2-hydroxy-phenyl)-4,5-dihydo-pyrazol-1-yl]-methanone (b17) was the most effective anticancer agent against HepG-2 cells owing to its notable inhibitory effect on HepG-2 with an IC50 value of 3.57 µM when compared with cisplatin (IC50 = 8.45 µM) and low cytotoxicity against primary hepatocytes. Cell cycle analysis and apoptosis/necrosis evaluation using this compound revealed that b17 notably arrested HepG-2 cells in the G2/M phase and induced HepG-2 cells apoptosis. Our findings indicate that compound b17 may be a promising anticancer drug candidate.

A Highly Selective and Efficient Copper(II) – “Turn‐On” Fluorescence Imaging Probe for l‐Cysteine

A simple copper(II) complex of the anthracenyl‐appended terpyridine ligand 4′‐(anthracen‐9‐yl)‐2,2′:6′,2′′‐terpyridine (L), [Cu(L)Cl2] (1, ESI‐MS, m/z = 507.08), is reported as a highly selective “turn‐on” optical imaging probe for l‐cysteine. Probe 1 shows a CuII/CuI redox potential [E1/2 = –0.194 V versus normal hydrogen electrode (NHE)] within a biologically viable range. The copper center in 1 adopts a square‐pyramidal geometry (τ = 0.0851), and the Cu–Npy bond (1.970 Å) of the middle pyridine (py) ring is shorter than the other two Cu–Npy bonds (2.069 and 2.040 Å). The Cu–Cl bonds (2.444 and 2.027 Å) are labile enough to be replaced by solvent molecules. The square‐based geometry is further supported by the A∥ value of 156.8 × 10–4 cm–1 determined by electron paramagnetic resonance (EPR) spectroscopy at 70 K. The d–d transition of 1 in acetonitrile/4‐(2‐hydroxyethyl)‐1‐piperazineethanesulfonic acid (acetonitrile/HEPES) buffer at pH 7.34 appears at λ =760 nm (ε = 198 m–1 cm–1), and the ligand‐based transitions are observed at λ = 327–384 nm. The ligand shows strong fluorescence at λ = 430 nm with a quantum yield of 11 %, but its emission intensity is completely quenched on coordination with Cu2+ ions, as in 1. Probe 1 detects l‐cysteine selectively through turn‐on fluorescence intensity at λem = 431 nm with a limit of detection of 1.9 × 10–8 m at pH 7.34. Interestingly, probe 1 is able to visualize exogenously added l‐cysteine in Henrietta Lack cervical cancer (HeLa) cells, human liver hepatocellular carcinoma (HepG2) cells, and human embryonic kidney 293 (HEK293) cells under identical conditions at pH 7.4 in confocal microscopy imaging.

Protective effects of an ethanol extract of Angelica keiskei against acetaminophen-induced hepatotoxicity in HepG2 and HepaRG cells.

BACKGROUND/OBJECTIVEAlthough Angelica keiskei (AK) has widely been utilized for the purpose of general health improvement among Asian, its functionality and mechanism of action. The aim of this study was to determine the protective effect of ethanol extract of AK (AK-Ex) on acute hepatotoxicity induced by acetaminophen (AAP) in HepG2 human hepatocellular liver carcinoma cells and HepaRG human hepatic progenitor cells.MATERIALS/METHODSAK-Ex was prepared HepG2 and HepaRG cells were cultured with various concentrations and 30 mM AAP. The protective effects of AK-Ex against AAP-induced hepatotoxicity in HepG2 and HepaRG cells were evaluated using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide, lactate dehydrogenase (LDH) assay, flow cytometry, and Western blotting.RESULTSAK-Ex, when administered prior to AAP, increased cell growth and decreased leakage of LDH in a dose-dependent manner in HepG2 and HepaRG cells against AAP-induced hepatotoxicity. AK-Ex increased the level of Bcl-2 and decreased the levels of Bax, Bok and Bik decreased the permeability of the mitochondrial membrane in HepG2 cells intoxicated with AAP. AK-Ex decreased the cleavage of poly (ADP-ribose) polymerase (PARP) and the activation of caspase-9, -7, and -3.CONCLUSIONSThese results demonstrate that AK-Ex downregulates apoptosis via intrinsic and extrinsic pathways against AAP-induced hepatotoxicity. We suggest that AK could be a useful preventive agent against AAP-induced apoptosis in hepatocytes.

Lipid-Modulating Effect of Black Lingzhi Medicinal Mushroom, Amauroderma rugosum (Agaricomycetes), on Oleate-Induced Human Hepatocellular Liver Carcinoma Cells.

Dyslipidemia is the key precursor of atherosclerotic cardiovascular disease. The aim of this study was to investigate the lipid-modifying potential of organic solvent-partitioned extracts from fruiting bodies of Amauroderma rugosum in vitro using oleate-induced human hepatocellular liver carcinoma (HepG2) cells. Our results demonstrated that oleate-induced HepG2 cells treated with ethyl acetate (EA) extract greatly decreased intracellular and secreted total triglyceride (TG) and total cholesterol (TC) compared with other extracts. Further investigation of cellular expression of selected apolipoproteins also revealed that oleate-induced HepG2 cells treated with the EA extract best attenuated the apolipoprotein (Apo) profile by downregulating ApoB-100 and ApoE while upregulating ApoA1. Because both ApoB-100 and ApoE are key components of low-density lipoprotein (LDL) and very LDL (VLDL), which are recognized as "bad cholesterol," this result indicates that treatment with the EA extract inhibited LDL and VLDL production in oleate-induced HepG2 cells. On the other hand, increasing ApoA1 evidence shows antiatherogenic benefits to increasing ApoA1, the key component of high-density lipoprotein (HDL), particularly in relation to its role in promoting reverse cholesterol transport and preventing LDL oxidation; this indicates that the EA extract upregulated the production of HDL ("good cholesterol"). Hence, the EA extract is a good source of lipid-ameliorating agents in the management of dyslipidemia.

Citral, A Monoterpene Protect Against High Glucose Induced Oxidative Injury in HepG2 Cell In Vitro-An Experimental Study.

Diabetes mellitus, a major metabolic disorder associated with hyperglycaemia is one of the leading cause of death in many developed countries. However, use of natural phytochemicals have been proved to have a protective effect against oxidative damage. To investigate the effect of citral, a monoterpene on high glucose induced cytotoxicity and oxidative stress in human hepatocellular liver carcinoma (Hep G2) cell line. Cells were treated with 50 mM concentration of glucose for 24 hours incubation following citral (30 μM) was added to confluent HepG2 cells. Cell viability, Reactive Oxygen Species (ROS) generation, DNA damage, lipid peroxidation, antioxidants and Mitogen Activated Protein Kinases (MAPKs) signaling were assessed in citral and/or high glucose induced HepG2 cells. Cells treated with glucose (50 mM), resulted in increased cytotoxicity, ROS generation, DNA damage, lipid peroxidation and depletion of enzymatic and non enzymatic antioxidants. In contrast, treatment with citral (30 μM) significantly decreased cell cytotoxicity, ROS generation, DNA damage, lipid peroxidation and increased antioxidants enzymes in high glucose induced HepG2 cells. In addition, the present study highlighted that high glucose treated cells showed increased expression of Extracellular Signal Regulated Protein Kinase-1 (ERK-1), c-Jun N-terminal Kinase (JNK) and p38 in HepG2 cells. On the other hand treatment with citral significantly suppressed the expression of ERK-1, JNK and p38 in high glucose induced HepG2 cells. Citral protects against high glucose induced oxidative stress through inhibiting ROS activated MAPK signaling pathway in HepG2 cells.

Graphene oxide as a nanocarrier for controlled release and targeted delivery of an anticancer active agent, chlorogenic acid

We have synthesized graphene oxide using improved Hummer's method in order to explore the potential use of the resulting graphene oxide as a nanocarrier for an active anticancer agent, chlorogenic acid (CA). The synthesized graphene oxide and chlorogenic acid-graphene oxide nanocomposite (CAGO) were characterized using Fourier transform infrared (FTIR) spectroscopy, thermogravimetry and differential thermogravimetry analysis, Raman spectroscopy, powder X-ray diffraction (PXRD), UV–vis spectroscopy and high resolution transmission electron microscopy (HRTEM) techniques. The successful conjugation of chlorogenic acid onto graphene oxide through hydrogen bonding and π–π interaction was confirmed by Raman spectroscopy, FTIR analysis and X-ray diffraction patterns. The loading of CA in the nanohybrid was estimated to be around 13.1% by UV–vis spectroscopy. The release profiles showed favourable, sustained and pH-dependent release of CA from CAGO nanocomposite and conformed well to the pseudo-second order kinetic model. Furthermore, the designed anticancer nanohybrid was thermally more stable than its counterpart. The in vitro cytotoxicity results revealed insignificant toxicity effect towards normal cell line, with a viability of >80% even at higher concentration of 50μg/mL. Contrarily, CAGO nanocomposite revealed enhanced toxic effect towards evaluated cancer cell lines (HepG2 human liver hepatocellular carcinoma cell line, A549 human lung adenocarcinoma epithelial cell line, and HeLa human cervical cancer cell line) compared to its free form.

Cytotoxic and Apoptotic Effects of Three Types of Silver-Iron Oxide Binary Hybrid Nanoparticles.

Multifunctional nanostructures have received great deal of attention in biomedical area due to their capabilities in the development of new therapeutic and diagnostic agents. Silver and iron oxide nanoparticles, owing to their specific characteristics, are considered to develop bifunctional hybrid nanoparticles for magnetic delivery of silver nanoparticles as cytotoxic agent toward cancer cells. This study was designed to explore the in-vitro cytotoxic and apoptotic activities of three different silver-iron oxide binary hybrid nanoparticles on human liver hepatocellular carcinoma cell line. Three different silver-iron oxide binary hybrid nanoparticles were synthesized and characterized through the designed procedures. Apoptosis induction was investigated through flow cytometry and the influence on bax gene expression level was analyzed using quantitative real time polymerase chain reaction. All the three types of silver-iron oxide hybrid nanoparticles (possessing different characteristics) exhibited cytotoxic and apoptotic effects. Furthermore, the up regulation of bax gene expression suggested the involvement of the intrinsic pathway of apoptosis. Some of the transcription regulators which could interact with bax gene promoter were analyzed and found out to be mostly contributed in the stress responses. Among the test nanoparticles, the strongest cytotoxic and apoptotic effect was induced by the binary hybrid nanoparticle which was synthesized with glucose as reducing agent; suggesting that the biological activity was affected by different characteristics of the designed nanoparticles. Combined properties of silver and magnetic nanoparticles in the binary hybrid nanoparticles, provide a great potential to be exploited in the cancer therapy, where the combination of cytotoxicity and magnetic targeting is desired.

Synthesis, crystal structures and biological evaluation of three ternary copper(II) complexes with fluorinated anthranilic acid derivatives

Three ternary copper(II) complexes [Cu(L1)(phen)] (1), [Cu(L2)(phen)] (2), and [Cu(L3)(phen)]·2H2O (3) (L1 = 4-fluoro-2-(picolinamido)benzoic acid, L2 = 4,5-difluoro-2-(picolinamido)benzoic acid, L3 = 4,5-difluoro-2-((2-hydroxybenzylidene)amino)benzoic acid, phen = 1,10-phenanthroline) have been synthesized and characterized by physicochemical and spectroscopic methods. In addition, X-ray crystallography showed that the Cu atoms in each of the complexes are five-coordinate, adopting distorted square pyramidal or trigonal bipyramidal geometries. The interactions of the complexes with calf-thymus DNA were investigated by UV absorption, fluorescence spectroscopy and viscosity measurements. In addition, the complexes were screened for in vitro cytotoxicity against A549 (human pulmonary carcinoma cells), Jurkat (human T lymphocyte cell line) and HepG-2 (human liver hepatocellular carcinoma cells); these experiments showed that complex 3 exhibited the most effective cytotoxicities (IC50 = 1.224–7.099 µM). Antibacterial studies revealed that complex 3 also exhibited highest activity, consistent with the DNA binding affinities.

In-vitro cytotoxicity and cellular uptake studies of luminescent functionalized core-shell nanospheres.

Monodispersed luminescent functionalized core-shell nanospheres (LFCSNs) were successfully synthesized and investigated for their cyto-toxic effect on human liver hepatocellular carcinoma cell line (HepG2 cells) by adopting MTT, DNA Ladder, TUNEL assay and qPCR based gene expressions through mRNA quantifications. The TUNEL and DNA ladder assays suggested an insignificant apoptosis in HepG2 cells due to the LFCSNs treatment. Further, the qPCR results also show that the mRNA expressions of cell cycle checkpoint gene p53 and apoptosis related gene (caspase-9) was up-regulated, while the antiapoptotic gene BCl-2 and apoptosis related genes FADD and CAS-3 (apoptosis effecter gene) were down-regulated in the LFCSNs treated cells. The nanospheres that were loaded into the cells confirm their intracellular uptake by light and fluorescent spectro-photometry and microscopy imaging analysis. The loaded nanospheres demonstrate an absolute resistance to photo-bleaching, which were applied for dynamic imaging to real-time tracking in-vitro cell migratory activity for continuous 24 and 48 h durations using a time-lapsed fluorescent microscope. These properties of LFCSNs could therefore promote applications in the area of fluorescent protein biolabeling and drug-delivery.

Synthesis and characterization of mesoporous magnetic nanocomposites wrapped with chitosan gatekeepers for pH-sensitive controlled release of doxorubicin

Multifunctional nanocarriers based on the Fe3O4 nanoparticles core and mesoporous silica shell (mSiO2) were synthesized for controlled drug release through magnetic targeting and pH-sensitive performances. The developed Fe3O4@mSiO2 nanocarriers exhibited a suitable size (63nm) and good magnetic responsibility, doxorubicin (DOX) could be successfully loaded into the mesoporous of Fe3O4@mSiO2 via electrostatic interaction, and the drug loading content and loading efficiency are 29.3% and 93.6%, respectively. The chitosan (CS) was employed to wrap the Fe3O4@mSiO2-DOX as the blocking agent to inhibit premature drug release, and the final CS/Fe3O4@mSiO2-DOX exhibited excellent pH-sensitivity, 86.1% DOX was released within 48h at pH4.0. Furthermore, all the release behaviors fit the Higuchi model very well and a purely diffusion-controlled process played a major role on DOX release from CS/Fe3O4@mSiO2-DOX. In addition, MTT assays in human liver hepatocellular carcinoma cells (HepG2) demonstrated that the CS/Fe3O4@mSiO2-DOX had high anti-tumor activity, while the Fe3O4@mSiO2 nanocarriers were practically non-toxic. Thus, our results revealed that the CS/Fe3O4@mSiO2-DOX could play an important role in the development of intracellular delivery nanodevices for cancer therapy.

Synthesis, characterization of 1,2,4-triazole Schiff base derived 3d-metal complexes: Induces cytotoxicity in HepG2, MCF-7 cell line, BSA binding fluorescence and DFT study

Two novel Schiff base ligands H2L1 and H2L2 have been synthesized by condensation reaction of amine derivative of 1,2,4-triazole moiety with 2-hydroxy-4-methoxybenzaldehyde. Co(II), Ni(II), Cu(II) and Zn(II) of the synthesized Schiff bases were prepared by using a molar ratio of ligand:metal as 1:1. The structure of the Schiff bases and synthesized metal complexes were established by 1H NMR, UV–Vis, IR, Mass spectrometry and molar conductivity. The thermal stability of the complexes was study by TGA. Fluorescence quenching mechanism of metal complexes 1–4 show that Zn(II) and Cu(II) complex binds more strongly to BSA. In DFT studies the geometries of Schiff bases and metal complexes were fully optimized with respect to the energy using the 6-31+g(d,p) basis set. The spectral data shows that the ligands behaves as binegative tridentate. On the basis of the spectral studies, TGA and DFT data an octahedral geometry has been assigned for Co(II), Ni(II), square planar for Cu(II) and tetrahedral for Zn(II) complexes. The anticancer activity were screened against human breast cancer cell line (MCF-7) and human hepatocellular liver carcinoma cell line (Hep-G2). Result indicates that metal complexes shows increase cytotoxicity in proliferation to cell lines as compared to free ligand.

Facile synthesis of magnetic-/pH-responsive hydrogel beads based on Fe3O4 nanoparticles and chitosan hydrogel as MTX carriers for controlled drug release

In the present study, methotrexate (MTX)-encapsulated magnetic-/pH-responsive hydrogel beads based on Fe3O4 nanoparticles and chitosan were successfully prepared through a one-step gelation process, which is a very facile, economic and environmentally friendly route. The developed hydrogel beads exhibited homogeneous porous structure and super-paramagnetic responsibility. MTX can be successfully encapsulated into magnetic chitosan hydrogel beads, and the drug encapsulation efficiency (%) and encapsulation content (%) were 93.8 and 6.28%, respectively. In addition, the drug release studies in vitro indicated that the MTX-encapsulated magnetic chitosan hydrogel beads had excellent pH-sensitivity, 90.6% MTX was released from the magnetic chitosan hydrogel beads within 48 h at pH 4.0. WST-1 assays in human liver hepatocellular carcinoma cells (HepG2) demonstrated that the MTX-encapsulated magnetic chitosan hydrogel beads had good cytocompatibility and high anti-tumor activity. Therefore, our results revealed that the MTX-encapsulated magnetic chitosan hydrogel beads would be a competitive candidate for controlled drug release in the area of targeted cancer therapy in the near future.

Enantioselective environmental behavior and cytotoxicity of chiral acaricide cyflumetofen

Enantioselective dissipation behavior of the new acaricide cyflumetofen (CYF) in citrus and soil, and its cytotoxicity to human liver hepatocellular carcinoma (HepG2) cells was investigated for the first time. The results of degradation experiment showed that roughly similar half-lives of (−)-CYF and (+)-CYF were achieved in citrus (16.5 and 19.8 d) and soil (6.37 and 6.99 d), respectively. EF values varied from 0.50 to 0.42 in citrus and from 0.49 to 0.48 in soil, indicating that slightly enantioselective degradation happened during experiment period. Moreover, indexes of MTT, LDH, ROS, MDA, SOD, and CAT were used to evaluate enantioselective cytotoxicity and oxidative stress of CYF enantiomers to HepG2 cells. Dose- and structure form-dependent phenomenon was observed with toxicity orders of (−)-CYF > rac-CYF > (+)-CYF. Despite the similar environmental degradation behavior, the toxicities of CYF enantiomers showed great difference, suggesting that (+)-CYF might be developed as potential substitute of rac-CYF for safety consideration.