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ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY · 2012 · IF 1.469

Study on cytotoxicity and structure–activity relationship of HL-7702 cell exposed to naphthoquinones

Jing Guo,Wenhua Song,Feng Ding,Jinyang Zhang,Zengtian Sun

The acute cytotoxicities of six naphthoquinone compounds, including Atovaquone, Buparvaquone, Menadione, 2-acetoxy-1,4-naphthoquinone and 2-ethoxy-1,4-naphthoquinone, to HL-7702 cells were determined. The results showed that the toxicities of these naphthoquinones were characterized by a steep response pattern except for 2-hydroxy-1,4-naphthoquinone. Meanwhile, the cellular injuries were unrecoverable. Several molecular descriptors, such as the octanol–water partition coefficients (Log   P ), diameter (Dia) and topological index (TIndx), played an important role in the toxicity of naphthoquinones to HL-7702 cell. Our results provide a foundation for further investigation using 3D-QSAR and HQSAR to evaluate the aquatic ecological risk and the possible mechanisms of toxicity of naphthoquinones.

研究领域: 毒理学 · 药理学 · 生物化学
✓ 已验证 DOI PubMed 高影响因子
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ARCHIVES OF PHARMACAL RESEARCH · 2015 ·Vol. 39 ·期 2 ·172-177 · IF 2.046

Xanthones from Garcinia paucinervis with in vitro anti-proliferative activity against HL-60 cells

Li Da-Hong,Li Chen-Xi,Jia Cui-Cui,Sun Ya-Ting,Xue Chun-Mei,Bai Jiao,Hua Hui-Ming,Liu Xiao-Qiu,Li Zhan-Lin

Three new xanthones, paucinervins H–J ( 1 – 3 ), as well as eleven known compounds ( 4 – 14 ), were isolated from the leaves of Garcinia paucinervis. The structures of the new compounds ( 1 – 3 ) were elucidated by 1D, 2D NMR spectra and HR ESIMS. In vitro antiproliferative activity against human promyelocytic leukemia HL-60 cells was tested, among which, compounds 2 , 5 , 6 and 7 exhibited strong growth inhibitory effects with GI 50 values ranging from 1.30 to 9.08 μM, respectively. Preliminary SARs were also discussed.

CAS / MDL: 51-21-8
研究领域: 药理学 · 植物化学 · 肿瘤学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF COLLOID AND INTERFACE SCIENCE · 2023 · IF 9.9

Fabrication of magnetic MnFe2O4@HL composites with an in situ Fenton-like reaction for enhancing tetracycline degradation

Weike Zhao,Bo Yang

Novel magnetic MnFe 2 O 4 @honey locust-derived carbon (MnFe 2 O 4 @HL) composites were synthesized via an in-situ hydrothermal precipitation method, and were characterized as an excellent Fenton-like catalyst for tetracycline (TC) degradation. Results showed that the vast majority of TC was mineralized in hydrogen peroxide (H 2 O 2 )/MnFe 2 O 4 @HL system after 120 min of reaction time with 92.3% of removal efficiency and the removal of 71.3% of total organic carbon (TOC). Systematic characterization approaches including scanning electron microscope (SEM), energy-dispersive X-ray spectrometry (EDS), X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS) and vibrating sample magnetometry (VSM) were introduced to reveal the microstructure and properties of magnetic MnFe 2 O 4 @HL composites. Hydroxyl radicals ( • OH) were identified as the major reactive oxygen species (ROS) via the quenching experiments and electron spin resonance (ESR) analysis, while superoxide radicals (·O 2 − ) played a negligible role. The dual cycles of both Fe 3+ /Fe 2+ and Mn 3+ /Mn 2+ were significant enhanced through the bimetallic redox effect and the electron transfer effect of the carbon-based functional group, accelerating the generation of • OH. The removal of TC was still up to 79.3% after five reuses of magnetic composites, demonstrating the MnFe 2 O 4 @HL with excellent stability and reuse performance. The influence of various experimental control conditions involving initial pH, catalyst and H 2 O 2 dosage, temperature, as well as common anions (Cl − , NO 3 − , and HCO 3 − ) on the degradation of TC were finally evaluated. This study provides an efficient in-situ generation method of emerging magnetic materials, and systematically reveals its mechanism of homogeneous Fenton-like catalysis, which shows promising applications for the degradation of environmental contaminants.

研究领域: 环境科学 · 材料科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ENVIRONMENTAL TOXICOLOGY · 2019 ·Vol. 34 ·期 5 ·666-673 · IF 2.649

8:2 Fluorotelomer alcohol causes G1 cell cycle arrest and blocks granulocytic differentiation in HL-60 cells

Xia Wang,Chenqian Zhou,Bingnan He,Baida Kong,Lai Wei,Rong Wang,Jiajia Lin,Yiyan Shao,Jianbo Zhu,Yuanxiang Jin,Zhengwei Fu

Fluorotelomer alcohols (FTOHs) are fluorinated intermediates used in manufacturing specialty polymer and surfactants, with 8:2 FTOH the homologue of largest production. FTOHs were found to pose acute toxicity, hepatotoxicity, nephrotoxicity, developmental toxicity and endocrine-disrupting risks, whereas research regarding immunotoxicity and its underlying mechanism, especially on specific immune cells is limited. Here, we investigated the immunotoxicity of 8:2 FTOH on immature immune cells in an in vitro system. We observed that exposure of HL-60 cells, a human promyelocytic leukemic cell line, to 8:2 FTOH reduced cell viability in a dose- and time-dependent manner. In addition, 8:2 FTOH exposure caused G1 cell cycle arrest in HL-60 cells, while it showed no effect on apoptosis. Exposure to 8:2 FTOH inhibited the mRNA expression of cell cycle-related genes, including CCNA1 , CCNA2 , CCND1 , and CCNE2 . Moreover, exposure to 8:2 FTOH inhibited the mRNA expression of granulocytic differentiation-related genes of CD11b , CSF3R , PU.1 , and C/EPBε in HL-60 cells . Furthermore, 8:2 FTOH exhibited no effect on intracellular ROS level, while hydralazine hydrochloride (Hyd), one reactive carbonyl species (RCS) scavenger, partially blocked 8:2 FTOH-caused cytotoxicity in HL-60 cells. Overall, the results obtained in the study show that 8:2 FTOH poses immunotoxicity in immature immune cells and RCS may partially underline its mechanism.

CAS / MDL: 304-20-1 678-39-7
研究领域: 毒理学 · 免疫学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Frontiers in Pharmacology · 2022 · IF 5.988

Therapeutic Effect of Ultrasound Combined With Porous Lipid Clioquinol/PLGA Microbubbles on Ferroptosis in HL-1 Cardiac Cell Induced by Isoproterenol Attack

Nana Li,Lei Dong,Yuanyuan Shen,Yongling Wang,Liansheng Chang,Hongwei Wu,Yuqiao Chang,Menghao Li,Dan Li,Zhaoyi Li,Mei He,Cheng Li,Yao Wei,Haiqin Xie,Feng Wang

In recent years, studies have shown a close relationship between cardiomyocyte death and ferroptosis. Clioquinol (CQ) can inhibit ferroptosis. Porous lipid-poly (lactic-co-glycolic acid) (PLGA) microbubbles (MBs) were prepared by double emulsification (W 1 /O/W 2 ) using 1,2-dioctadecanoyl-sn-glycero-3-phophocholine and PLGA as raw materials. Porous lipid-PLGA MBs were used as carriers to prepare CQ/PLGA MBs containing CQ. CQ/PLGA had the advantages of high drug loading, good biocompatibility, and sustained release. Our results showed that CQ/PLGA improved the effect of CQ and reduced its cytotoxicity. Under low-frequency ultrasound with certain parameters, CQ/PLGA showed steady-state cavitation, which increased the membrane permeability of mouse cardiomyocyte HL-1 to a certain extent and further prevented the process of ferroptosis in mouse cardiomyocyte HL-1.

研究领域: 心脏病学 · 药学 · 生物医学工程
✓ 已验证 DOI PubMed 高影响因子
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Anti-Cancer Agents in Medicinal Chemistry · 2013 ·Vol. 13 ·期 8 ·1280-1290 · IF 2.61

Glaucocalyxin A and B-induced Cell Death is Related to GSH Perturbation in Human Leukemia HL-60 Cells

Wen Hua Yang,Zhen Zhang,Yang Hu Sima,Jian Zhang,Jian Wen Wang

Glaucocalyxin (Gla) A-C are major ent-kauranoid diterpenoids isolated from Rabdosia japonica var. glaucocalyx, a plant used in Chinese traditional medicine as an antitumor and anti-inflammatory agent. The present investigation was carried out to observe whether cellular reduced glutathione (GSH) plays important roles in Gla -induced cytotoxicity. Among major ent-kauranoid diterpenoids isolated, Gla A and B dose-dependently decreased the growth of HL-60 cells with an IC50 of approximately 6.15 and 5.86 µM at 24 h, respectively. Both Gla A and B could induce apoptosis, G2/M-phase cycle arrest, DNA damage and the accumulation of reactive oxygen species (ROS) in HL-60 cells. Moreover, Gla A, B caused rapid decrease of the intracellular GSH content, while inhibition of cellular GSH synthesis by buthionine sulfoximine (BSO) augmented the induced cytotoxicity and apoptosis in HL-60 cells. On the other hand, the administration of GSH or GSH precursor N-acetyl-cysteine (NAC) could rescue Gla A, B-depleted cellular GSH, and abrogate the induced cytotoxicity, G2/M-phase cycle arrest, DNA damage and ROS accumulation in HL-60 cells. Furthermore, Gla A, B decreased the activity of the GSH-related enzymes including glutathione reductase (GR) and glutathione peroxidase (GPX). These data suggest that the intracellular GSH redox system plays important roles in regulating the Gla A, B-induced cytotoxicity on HL-60 cells.

研究领域: 药理学 · 生物化学 · 肿瘤学 · 细胞生物学 · 天然产物化学
✓ 已验证 DOI 高影响因子
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BIOSENSORS & BIOELECTRONICS · 2016 · IF 7.476

Ultrasensitive and selective assay of glutathione species in arsenic trioxide-treated leukemia HL-60 cell line by molecularly imprinted polymer decorated electrochemical sensors

Bo Zhang,Jie Liu,Xiaoru Ma,Peng Zuo,Bang-ce Ye,Yingchun Li

Herein a pair of molecularly imprinted polymer (MIP) modified electrochemical sensors were reported to detect glutathione (GSH) and glutathione disulfide (GSSG) in arsenic trioxide-treated HL-60 cells. MIP film was in situ synthesized onto electrode surface via electro-polymerization in a facile way. The characteristics of the obtained sensors were investigated by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Both GSH-MIP and GSSG-MIP sensors exhibit the relatively wide linear detection range and low detection limit of 1.33×10 −10   M (S/N=3). It is found that N-acetylcysteine and DL-homocysteine, the precursors of GSH, show little influence on the detection of glutathione species, nor did the reactants of arsenite and GSH. Such strategies were successfully applied to discriminate GSH and GSSG in cell samples with acceptable recoveries of 92.0–109.1%, and the results are comparable with classic o -phthalaldehyde fluorospectrophotometry. Moreover, the presented sensors allow for easy disclosure of the reversion of malignant phenotype in leukemia cells via glutathione species analysis.

CAS / MDL: 95-54-5
研究领域: 分析化学 · 医学 · 生物化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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PROTEIN EXPRESSION AND PURIFICATION · 2015 · IF 1.695

A stereoselective esterase from Bacillus megaterium: Purification, gene cloning, expression and catalytic properties

Jian-yong Zheng,Jian Wang,Sha-sha Zhou,Xiao-jun Li,Xiang-xian Ying,Zhao Wang

Esterases (EC 3.1.1.X) have been used as biocatalysts due to their good stability, high chemo-, regio- and stereoselectivity. In our previous studies, Bacillus megaterium WZ009 harboring esterase displayed the unique capability to convert ( S )-4-Chloro-3-hydroxyethylbutyrate (CHBE) in the racemate to ( S )-3-hydroxy-γ-butyrolactone (HL) through stereoselective hydrolysis, dechlorination, and lactonization. The remaining ( R )-CHBE and formed ( S )-HL could be obtained in a one-pot enzymatic reaction. An esterase from B. megaterium WZ009 was purified and was found to have 466 encoded amino acids and an apparent molecular mass of 55 kDa. The purified esterase exhibited maximal activity at a temperature of 25 °C and at a pH of 11.5 towards 100 mM CHBE. When the stereoselective biocatalysis of rac -CHBE was performed using the recombinant Escherichia coli BL21 (DH3) cells harboring the esterase, the catalytic activity increased by 20-fold compared with the original strain B. megaterium WZ009. With the addition of activated carbon (62 g/L) in the reaction system, the conversion was increased from 39% to 45% at a substrate concentration of 750 mM. Another remarkable advantage is that both of the obtained residual ( R )-CHBE and the formed ( S )-HL had high optical purities ( e.e. s  > 99.9%, e.e. p  > 99.9%), thereby making this esterase a usable biocatalyst for industrial application.

CAS / MDL: 4046-02-0
研究领域: 生物化学 · 分子生物学 · 工业酶学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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MOLECULES · 2019 ·Vol. 24 ·期 7 ·1211 · IF 3.06

In Vitro Toxicity Study of a Porous Iron(III) Metal‒Organic Framework

Gongsen Chen,Xin Leng,Juyuan Luo,Longtai You,Changhai Qu,Xiaoxv Dong,Hongliang Huang,Xingbin Yin,Jian Ni

A MIL series metal‒organic framework (MOF), MIL-100(Fe), was successfully synthesized at the nanoscale and fully characterized by TEM, TGA, XRD, FTIR, DLS, and BET. A toxicological assessment was performed using two different cell lines: human normal liver cells (HL-7702) and hepatocellular carcinoma (HepG2). In vitro cytotoxicity of MIL-100(Fe) was evaluated by the MTT assay, LDH releasing rate assay, DAPI staining, and annexin V/PI double staining assay. The safe dose of MIL-100(Fe) was 80 μg/mL. It exhibited good biocompatibility, low cytotoxicity, and high cell survival rate (HL-7702 cells’ viability >85.97%, HepG2 cells’ viability >91.20%). Therefore, MIL-100(Fe) has a potential application as a drug carrier.Keywords:MIL-100(Fe);in vitro toxicity;HL-7702 cells;HepG2 cells

CAS / MDL: 7439-89-6
研究领域: 材料科学 · 毒理学 · 生物医学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Oxidative Medicine and Cellular Longevity · 2021 · IF 6.543

Preclinical Evaluation of Safety, Pharmacokinetics, Efficacy, and Mechanism of Radioprotective Agent HL-003

Yahong Liu,Longfei Miao,Yuying Guo,Hongqi Tian

Amifostine is a radioprotector with high efficacy but poor safety, short half-life, no oral formulation, and poor compliance, which limits its application. With the increasing risk of exposure to radiation, the development of new radioprotective agents is critical. We previously synthesized a new amifostine derivative, the small molecule compound HL-003. In this study, we focused on evaluating the radioprotective properties of HL-003. Using the in vitro 2,2-diphenyl-1-picrylhydrazyl assay, we initially confirmed HL-003 as a strong antioxidant and demonstrated that its free radical scavenging activity was stronger than that of amifostine. Then, we performed an acute toxicity test, a 28-day toxicity test, a 30-day survival rate test, and a pharmacokinetic study, all of which provided aggregate evidence that HL-003 functioned as a small molecule radioprotector with high efficacy, a favorable safety profile, a long half-life, and oral administration. The intestinal radioprotective mechanism of HL-003 was explored in male C57 mice after abdominal irradiation by analyzing intestinal tissue samples with hematoxylin-eosin staining, immunohistochemistry, TUNEL staining, and immunofluorescence detection. The results showed that HL-003 protected intestinal DNA from radiation damage and suppressed the expression of phosphorylated histone H2AX, phosphorylated p53, and the apoptosis-related proteins caspase-8 and caspase-9, which contributed to maintaining the normal morphology of the small intestine and provided insights into the mechanism of radioprotection. Thus, HL-003 is a small molecule radioprotector with a potential application in radiation medicine.

研究领域: 放射医学 · 药理学 · 毒理学 · 分子生物学
✓ 已验证 DOI PubMed 高影响因子
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ANALYTICAL CHEMISTRY · 2024 · IF 6.7

Determination of Acetylamantadine by γ-Cyclodextrin-Assisted α-HL Nanopore for Potential Cancer Prediagnosis

Yun-Dong Yin,Lei Yang,Xi-Tong Song,Jun Hu,Fang-Fang Chen,Ming Xu,Zhi-Yuan Gu

The high expression of Spermidine/spermine N1-acetyltransferase (SSAT-1) is an important indicator in early cancer diagnosis. Here, we developed a nanopore-based methodology with γ-cyclodextrin as an adaptor to detect and quantify acetylamantadine, the specific SSAT-1-catalyzed product from amantadine, to accordingly reflect the activity of SSAT-1. We employ γ-cyclodextrin and report that amantadine cannot cause any secondary signals in γ-cyclodextrin-assisted α-HL nanopore, while its acetylation product, acetylamantadine, does. This allows γ-cyclodextrin to practically detect acetylamantadine in the interference of excessive amantadine, superior to the previously reported β-cyclodextrin. The quantification of acetylamantadine was not interfered with even a 50-fold amantadine and displayed no interference in artificial urine sample analysis, which indicates the good feasibility of this nanopore-based methodology in painless cancer prediagnosis. In addition, the discrimination mechanism is also explored by 2-D nuclear magnetic resonance (NMR) and nanopore experiments with a series of adamantane derivatives with different hydrophilic and hydrophobic groups. We found that both the hydrophobic region matching effect and hydrophilic interactions play a synergistic effect in forming a host–guest complex to further generate the characteristic signals, which may provide insights for the subsequent design and study of drug-cyclodextrin complexes.

研究领域: 生物化学 · 医学诊断 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CHEMOSPHERE · 2017 · IF 4.208

Cellular responses of normal (HL-7702) and cancerous (HepG2) hepatic cells to dust extract exposure

Ping Xiang,Rui-Wen He,Rong-Yan Liu,Kan Li,Peng Gao,Xin-Yi Cui,Hongbo Li,Yungen Liu,Lena Q. Ma

Cancerous human liver cell line has been used to test the hepatic toxicity of indoor dust, showing its organic extract decreases cell viability. However, little is known about its impact on normal human liver cell line. In the present study, we compared the cellular responses between carcinoma cell line (HepG2) and normal cell line (HL-7702) after exposing to 10–640 μg/100 μL organic dust extract for 24 h. The dust extract caused cytotoxicity, oxidative damage, inflammatory response and loss of mitochondrial transmembrane potential (MMP) in both cells. The inhibition of cell viability in HL-7702 cells was stronger than that in HepG2 cells, with HL-7702 cells having lower LC 50 . Higher production of oxidative stress , more loss of MMP and stronger suppression of antioxidant enzymes mRNA level occurred in HepG2 cells, while mRNA expression and hepcidin secretion were enhanced in HL-7702 cells at 40/100 μL, indicating the dust extract probably perturbed their liver Fe homeostasis . Our data showed considerable differences in cellular responses between normal and cancerous cell lines. To obtain accurate data, normal hepatocytes should be employed as they better match with the in vivo tissue than cancerous cell lines.

研究领域: 毒理学 · 细胞生物学 · 环境健康
✓ 已验证 DOI PubMed 高影响因子
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