Food & Function
·
2016
·Vol. 7
·期 11
·4683-4692
·
IF 2.686
Fan Yuan-jing,Wei Wei,Luo Jian-ping,Jin Yu-xia,Dai Zi-ling
This study aimed to explore the effects of genistein on regulating the activation of UGTs via the Nrf2/Keap1 pathway and to elucidate the underlying mechanisms of detoxification and hepatic protection. Experiments monitoring genistein-induced protection against acetaminophen-induced cell damage were performed in L-02, HepG2 and Hep3b cells. The results of the MTT, AST, ALT, LDH, GSH and GSSG assays showed that genistein evidently protected the cells from acetaminophen-induced injury in a dose-dependent manner. The control cells were treated with 10 mM acetaminophen without genistein to compare with the effects of the combination of acetaminophen and genistein on the expression of UGT1A1, 1A6 and 1A9, Nrf2 and Keap1 mRNAs, as well as the expression of Nrf2 and Keap1 proteins, which were tested by western blotting. The results showed that the expression of the Nrf2 mRNA and protein increased; in contrast, the expression levels of the Keap1 mRNA and protein were obviously reduced by genistein in a dose-dependent manner. Meanwhile, the expression of the UGT mRNA was increased, and UGT1A9 exhibited the highest expression among the three UGTs. Accordingly, the residual acetaminophen content was obviously reduced and acetaminophen glucuronidation increased after 24 hours of treatment with genistein in a dose-dependent manner.
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高影响因子
TALANTA
·
2017
·
IF 4.162
Bin Yang,Yuan Zhang,Beibei Chen,Man He,Bin Hu
This work reports an efficient, specific and sensitive immunoassay protocol for detection of tumor cells by using inductively coupled plasma mass spectrometry (ICP-MS) with lead sulfide nanoparticles (PbS NPs) as the elemental tags. PbS NPs conjugated with anti-EpCAM target the HepG2 cells with high affinity and specificity. The conditions of the ICP-MS based immunoassay for the detection of HepG2 cells were carefully optimized, including the incubation time, the concentration of the labeling probe, and the elution conditions. Under the optimized conditions, the limit of detection of 282 HepG2 cells and the linear range of 800–40,000 were obtained, and the relative standard deviation for seven replicate determinations of 3000 HepG2 cells was 5.0%. The proposed method has numerous advantages, including ease of preparation, high sensitivity and selectivity. Importantly, this methodology could be extended to the detection of other cells based on their cellular biomarkers.
研究领域:
生物医学工程
·
分析化学
·
癌症研究
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高影响因子
CURRENT PHARMACEUTICAL BIOTECHNOLOGY
·
2023
·
IF 2.8
Chang Chun-hui,Han De-en,Ji Yu-ying,Wang Meng-yan,Li Dong-hong,Xu Zhi-ling,Li Jia-hao,Huang Sheng-nan,Zhu Xia-li,Jia Yong-yan
Background: Although quercetin exhibits promising anti-tumor properties, its clinical
application is limited due to inherent defects and a lack of tumor targeting.
Objective: This study aimed to prepare and characterize active targeting folate-chitosan modified
quercetin liposomes (FA-CS-QUE-Lip), and its antitumor activity in vitro and in vivo was also
studied.
Methods: Box-Behnken Design (BBD) response surface method was used to select the optimal
formulation of quercetin liposomes (QUE-LP). On this basis, FA-CS-QUE-LP was obtained by
connecting folic acid chitosan complex (FA-CS) and QUE-LP. The release characteristics in vitro
of QUE-LP and FA-CS-QUE-LP were studied. Its inhibitory effects on HepG2 cells were studied
by the MTT method. The pharmacokinetics and pharmacodynamics in vivo were studied in
healthy Wistar mice and S180 tumor-bearing mice, respectively.
Results: The average particle size, zeta potential and encapsulation efficiency of FA-CS-QUELP
were 261.6±8.5 nm, 22.3±1.7 mV, and 98.63±1.28 %, respectively. FA-CS-QUE-LP had a
sustained release effect and conformed to the Maloid-Banakar release model (R2=0.9967). The
results showed that FA-CS-QUE-LP had higher inhibition rates on HepG2 cells than QUE-Sol
(P<0.01). There was a significant difference in AUC, t1/2, CL and other pharmacokinetic parameters
among QUE-LP, FA-CS-QUE-LP, and QUE-Sol (P<0.05). In in vivo antitumor activity
study, the weight inhibition rate and volume inhibition rate of FA-CS-QUE-LP were 30.26% and
37.35%, respectively.
Conclusion: FA-CS-QUE-LP exhibited a significant inhibitory effect on HepG2 cells, influenced
the pharmacokinetics of quercetin in mice, and demonstrated a certain inhibitory effect on S180
tumor-bearing mice, thus offering novel avenues for cancer treatment.
研究领域:
药学
·
肿瘤学
·
药物递送系统
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高影响因子
XENOBIOTICA
·
2025
·
IF 1.2
Junling Zhu,Rilian Lai,Qin Zheng,Shuying Huang,Shenghua Hu,Zhangfei Xu,Huixia Sun
1. To study the effects of calycosin on palmitic acid-induced HepG2 cells, as well as the potential mechanisms of action.2. Potential targets of calycosin for the alleviation of insulin resistance were predicted by network pharmacology. Glucose concentration in the culture medium was determined by the GOD-POD method. The model of insulin resistance was established by palmitic acid-induced HepG2 cells. Effects of palmitic acid and calycosin on HepG2 cell activity were determined using an MTT assay kit. The expression levels of AKT1 and FOXO3a were detected by western blot.The expression level of hsa-miR-324-3p was detected by RT-qPCR. Dual luciferase reporter assay to detect targeting of AKT1 by hsa-miR-324-3p.3. AKT1 was predicted and validated as a potential target of calycosin for treatment of insulin resistance. The model of insulin resistance was successfully established by palmitic acid-induced HepG2 cells. Up-regulation of AKT1 expression inhibits FOXO3a entry into the nucleus. Calycosian was demonstrated to concentration-dependently increase the sensitivity of insulin resistance cells to insulin. The hsa-miR-324-3p was proven to exist in insulin-resistant cells. Hsa-miR-324-3p was found to target AKT1 involved in the alleviation of insulin resistance.4. Calycosin inhibits FOXO3a nuclear translocation by regulating the hsa-miR-324-3p/AKT pathway, thus alleviating insulin resistance.
研究领域:
药理学
·
分子生物学
·
内分泌学
·
细胞生物学
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2019
·Vol. 20
·期 20
·5074
·
IF 4.183
Mingzhuo Cao,Yong Gao,Mengling Zhan,Nasha Qiu,Ying Piao,Zhuxian Zhou,Youqing Shen
In the last 2–3 decades, gene therapy represented a promising option for hepatocellular carcinoma (HCC) treatment. However, the design of safe and efficient gene delivery systems is still one of the major challenges that require solutions. In this study, we demonstrate a versatile method for covalent conjugation of glycyrrhizin acid (GL) or glycyrrhetinic acid (GA) to increase the transfection efficiency of Polyethyleneimine (PEI, Mw 1.8K) and improve their targeting abilities of hepatoma carcinoma cells. GA and GL targeting ligands were grafted to PEI via N-acylation, and we systematically investigated their biophysical properties, cytotoxicity, liver targeting and transfection efficiency, and endocytosis pathway trafficking. PEI-GA0.75, PEI-GL10.62and PEI-GL20.65conjugates caused significant increases in gene transfection efficiency and superior selectivity for HepG2 cells, with all three conjugates showing specific recognition of HepG2 cells by the free GA competition assay. The endocytosis inhibition and intracellular trafficking results indicated that PEI-GA0.75and GL10.62conjugates behaved similarly to SV40 virus, by proceeding via the caveolae- and clathrin-independent mediated endocytosis pathway and bypassing entry into lysosomes, with an energy independent manner, achieving their high transfection efficiencies. In the HepG2 intraperitoneal tumor model, PEI-GA0.75and PEI-GL10.62carrying the luciferase reporter gene gained high gene expression, suggesting potential use for in vivo application.Keywords:gene therapy;glycyrrhizin acid;glycyrrhetinic acid;hepatic tumor targeting;caveolae- and clathrin-independent pathway;HepG2 intraperitoneal tumor model
研究领域:
药理学
·
分子生物学
·
基因治疗
·
癌症研究
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Applied Materials Today
·
2024
·
IF 7.2
Rui Deng,Jibin Wu,Baokang Zhu,Gaoqing Song,Tao Zhou,Musheng Yang,Lingling Pan,Jian Wang,Xuan Zou,Ziquan Lv,Xiaobao Jin,Yinghua Xu,Xuemei Lu,Shuiqing Gui
Hepatocellular carcinoma (HCC) has emerged as one of the most prevalent and highly malignant tumor malignancies worldwide and is characterized by poor prognosis and high mortality. Therefore, effective medications are urgently needed to improve therapeutic effects with HCC. Exosomes are nanoscale vesicles that can transfer cellular information. Owing to their excellent biocompatibility, exosomes are frequently utilized as drug carriers for cancer treatment. Targeted drug delivery systems that modify exosomes to increase targeting have emerged as promising therapeutic platforms in response to the lack of precise targeting by natural exosomes. In this study, HTPP-Exo was successfully constructed by modifying the exosome membrane by connecting sulfhydryl group of HTPP with maleimide in DSPE-PEG2000-Mal, and the antimicrobial peptide M1–8 was included for the first time through co-incubation, thus successfully establishing the HTPP-Exo-M1–8 targeted drug delivery system. The targeting ability of HTPP-Exo-M1–8 was verified by evaluating its in vitro and in vivo targeting of HepG2 cells, and its therapeutic ability was evaluated by its inhibitory effect on HepG2 cells and in situ liver cancer in mice. The results showed that HTPP-Exo-M1–8 targeted drug delivery system could target HepG2 cells in vivo and in vitro , and the survival rate of HepG2 cells was 45 % after HTPP-Exo-M1–8 treatment for 48 h. After in vivo treatment, the volume of HCC in HTPP-Exo-M1–8 group (270.4 mm 3 ) was much smaller than that in control group (969.5 mm 3 ), which achieved the expected purpose of HCC treatment. Further research showed that the targeted drug delivery system HTPP-Exo-M1–8 could be used to treat HCC by inhibiting the lysosome–autophagosome fusion in HepG2 cells. Additionally, there was no obvious toxicity to healthy cells or tissues when HTPP-Exo-M1–8 was used. Overall, the exosome-based targeted drug delivery system HTPP-Exo-M1–8 can treat HCC by targeting and penetrating tumor cells, which provides a new strategy for the treatment of HCC.
研究领域:
肿瘤学
·
药学
·
生物技术
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高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Chun-ge Zhang,Qiao-ling Zhu,Yi Zhou,Yang Liu,Wei-liang Chen,Zhi-Qiang Yuan,Shu-di Yang,Xiao-feng Zhou,Ai-jun Zhu,Xue-nong Zhang,Yong Jin
N-Succinyl-chitosan (NSC) was synthesized and NSC nanoparticles (NPs) with loaded osthole (Ost) (Ost/NSC-NPs) were prepared by emulsion solvent diffusion. Subsequently, low-density lipoprotein (LDL)-mediated NSC-NPs with loaded Ost (Ost/LDL-NSC-NPs) were obtained by coupling LDL with Ost/NSC-NPs through amide linkage. The average particle size of Ost/NSC-NPs was approximately 145 nm, the entrapment efficiency was 78.28%±2.06%, and the drug-loading amount was 18.09%±0.17%. The release of Ost from Ost/NSC-NPs in vitro showed a more evident sustained effect than the native material. The half maximal inhibitory concentration of Ost/LDL-NSC-NPs was only 16.23% that of the free Ost at 24 hours in HepG2 cells. Ost inhibited HepG2 cell proliferation by arresting cells in the synthesis phase of the cell cycle and by triggering apoptosis. Cellular uptake and subcellular localization in vitro and near-infrared fluorescence real-time imaging in vivo showed that Ost/LDL-NSC-NPs had high targeting efficacy. Therefore, LDL-NSC-NPs are a promising system for targeted Ost delivery to liver tumor.
研究领域:
药理学
·
药物递送
·
癌症研究
·
分子生物学
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COLLOIDS AND SURFACES B-BIOINTERFACES
·
2015
·
IF 4.152
Man Li,Min Gao,Yunlan Fu,Chao Chen,Xuan Meng,Aiping Fan,Deling Kong,Zheng Wang,Yanjun Zhao
On-demand curcumin delivery via stimuli-responsive micellar nanocarriers holds promise for addressing its solubility and stability problem. Polymer-curcumin prodrug conjugate micelle is one of such nanosystems. The diversity of linker and conjugation chemistry enabled the generation and optimization of different curcumin micelles with tunable stimuli-responsiveness and delivery efficiency. The aim of the current work was to generate and assess acetal-linked polymeric micelles to enrich the pH-responsive curcumin delivery platforms. Curcumin was slightly modified prior to conjugating to amphiphilic methoxy poly(ethylene glycol)-poly(lactic acid) (mPEG-PLA) copolymer via an acetal bond, whereas an ester bond-linked conjugate was used as the control. The acetal-containing micelles showed a hydrodynamic diameter of 91.1 ± 2.9 (nm) and the accompanying core size of 63.5 ± 7.1 (nm) with a zeta potential of −10.9 ± 0.7 (mV). Both control and pH-labile micelles displayed similar critical micelle concentration at 1.6 μM. The acetal-containing nanocarriers exhibited a pH-dependent drug release behavior, which was faster at lower pH values. The cytotoxicity study in HepG2 cells revealed a significantly lower IC 50 at 51.7 ± 9.0 (μM) for acetal-linked micelles in contrast to the control at 103.0 ± 17.8 (μM), but the polymer residue showed no cytotoxicity upon drug release. The acetal-linked micellar nanocarrier could be a useful addition to the spectrum of currently available stimuli-responsive curcumin nano-formulations.
研究领域:
药学
·
纳米技术
·
药物递送系统
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高影响因子
BIOFACTORS
·
2019
·Vol. 45
·期 4
·563-574
·
IF 3.598
Fuqiang Liang,Weiwei Cao,Yuting Huang,Yajing Fang,Yuxin Cheng,Siyi Pan,Xiaoyun Xu
Isoflavones are one group of the major flavonoids and possess multiple biological activities due to their antioxidant properties. However, a clear antioxidant mechanism of dietary isoflavones is still remained to be answered. In this study, the effects of isoflavones on the nuclear factor E2-related factor 2 (Nrf2)–antioxidant response element (ARE) signaling pathway and the underlying molecular mechanisms were investigated. Results showed that isoflavones are potential Nrf2–ARE activators while their activities were structure dependent. Biochanin A (BCA), an O -methylated isoflavone with low direct antioxidant activity, can effectively protect HepG2 cells against tert -butyl hydroperoxide ( t -BHP)-induced oxidative damage via activation of the Nrf2 signaling, and thereby the induction of downstream cytoprotective enzymes including NAD(P)H quinone oxidoreductase-1, heme oxygenasae-1, and glutamate-cysteine ligase catalytic subunit. A molecular docking study revealed that BCA could directly bind into the pocket of Kelch-like erythroid cell-derived protein with CNC homology (ECH)-associated protein 1 (Keap1), a cytoplasmic suppressor of Nrf2, to facilitate Nrf2 activation. The upstream mitogen-activated protein kinase (MAPK) pathways were also involved in the activation of Nrf2 signaling. These findings indicate that the protective actions of dietary isoflavones against oxidative damage may be at least partly due to their ability to enhance the intracellular antioxidant response system by modulating the Nrf2−ARE signaling pathway.
研究领域:
药理学
·
细胞生物学
·
分子生物学
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高影响因子
MOLECULES
·
2022
·Vol. 27
·期 12
·3940
·
IF 4.927
Dongge Yin,Xueling Hu,Mengru Cai,Kaixin Wang,Hulinyue Peng,Jie Bai,Yvchen Xv,Tingting Fu,Xiaoxv Dong,Jian Ni,Xingbin Yin
Curcumin (CUR) has a bright future in the treatment of cancer as a natural active ingredient with great potential. However, curcumin has a low solubility, which limits its clinical application. In this study, IRMOF-10 was created by the direct addition of triethylamine, CUR was loaded into IRMOF-10 using the solvent adsorption method, and the two were characterized using a scanning electron microscope (SEM), X-ray diffraction (XRD), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TG) methods, and Brunauer–Emmett–Teller (BET) analysis. We also used the MTT method, 4′,6-diamidino-2-phenylindole (DAPI) staining, the annexin V/PI method, cellular uptake, reactive oxygen species (ROS), and the mitochondrial membrane potential (MMP) to perform a safety analysis and anticancer activity study of IRMOF-10 and[email protected]on HepG2 cells. Our results showed that[email protected]had a CUR load of 63.96%, with an obvious slow-release phenomenon. The CUR levels released under different conditions at 60 h were 33.58% (pH 7.4) and 31.86% (pH 5.5). Cell experiments proved that IRMOF-10 was biologically safe and could promote curcumin entering the nucleus, causing a series of reactions, such as an increase in reactive oxygen species and a decrease in the mitochondrial membrane potential, thereby leading to cell apoptosis. In summary, IRMOF-10 is an excellent drug carrier and[email protected]is an effective anti-liver cancer sustained-release preparation.Keywords:MOFs;IRMOF-10;curcumin;HepG2 cells
研究领域:
药学
·
纳米技术
·
癌症研究
·
材料科学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Yanmei Yang,Jie Wang,Yan Zhang,Weijiao Xue,Yongfang Chen,Jiayu Yue,Yanqiao Wen,Ruofei Feng,Chunxia Tan
Ionized, phosphorylated (ASP P) and cationised (ASP N) derivatives of Angelica sinensis polysaccharide (ASP) were evaluated for their antitumour activity. We performed the CCK-8 assay, flow cytometry, scratch healing assay and fluorescence staining assay to detect the effects of different chemical modifications of ASP on the antitumour activity of HepG2 and Huh7 cells. Western blot was performed to detect the mechanism of antitumour effect. The results showed that ASP-P and ASP-N with maximum test concentration (240 μg·mL −1 ) had strong inhibitory effects on HepG2 cells with inhibition rates of 52.36 % and 31.76 %, respectively. Both ASP-P and ASP-N all significantly inhibited the proliferation and migration of HepG2 and Huh7 cells. Furthermore, the study revealed that both ASP-P and ASP-N up-regulated apoptosis related proteins, such as Caspase-3, Caspase-9, cleaved-caspase 9, Apaf-1, Bid, Bax, Caspase-8, FADD, Fas and down-regulated the expression of Bcl-2 to induce apoptosis in HepG2 and Huh7 cells. This observation was further corroborated by the identification of cell-cycle arrest-associated proteins CDK4, p53 and p21, where the expression of CDK4 was down-regulated, and the expression of p53 and p21 were up-regulated. Overall, ASP-P and ASP-N inhibits proliferation and migration and induces apoptosis of HepG2 and Huh7 cells by regulating the mitochondrial apoptotic pathway to achieve antitumor activity. ASP-P and ASP-N solution was injected by subcutaneous in the nude mice bearing tumors. In comparison with the control group, ASP-P and ASP-N were found to retard tumor growth to a significant extent without exerting any influence on the body weights of mice. The ASP-N group demonstrated the most favorable outcomes, exhibiting the lowest tumor volume.
研究领域:
药理学
·
肿瘤学
·
分子生物学
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高影响因子
JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
·
2023
·
IF 4.1
Bowei Du,Chao Zhang,Guiya Deng,Shuai Zhang,Shiqi Wang,Yuepeng Guan,Yaqin Huang
Background Nowadays, the prevalence of oxidative stress-related chronic diseases is increasing. The identification of novel antioxidant collagen-peptides to counteract oxidative stress for individuals’ health have gained significant intention. Results In this study, the collagen-peptides with antioxidant activities were separated and identified by ion chromatography (IEC), reversed-phase high-performance liquid chromatography (RP-HPLC), and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The identified antioxidant collagen-peptides were further screened by molecular docking for Keap1-targeted peptide inhibitors and their theoretical interaction mechanisms were investigated. Four novel antioxidant collagen-peptides, GPAGPIGPVG, GPAGPpGPIG, ISGPpGPpGPA and IDGRPGPIGPA with high binding affinity to Keap1 were selected. Molecular docking results demonstrated that the putative antioxidant mechanism of four antioxidant collagen-peptides contributed to their blockage of Keap1-Nrf2 interactions. The results of antioxidant activity of four antioxidant collagen-peptides proved that IDGRPGPIGPA exerted a high scavenging capacity to DPPH and ABTS free radicals, while GPAGPpGPIG improved the resistance of cells to hydrogen peroxide (H 2 O 2 ) induced oxidative damage by promoting the activation of intracellular antioxidant enzymes and the production of reduced glutathione in human hepatoma (HepG2) cells. Conclusion The antioxidant collagen-peptides (GPAGPIGPVG, GPAGPpGPIG, ISGPpGPpGPA and IDGRPGPIGPA) will be developed as the novel functional food for human health in the near future. This article is protected by copyright. All rights reserved.
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