ACS Omega
·
2023
·
IF 4.1
Zihan He,Haoying Song,Jingjing Cheng,Wenxiu Qiu,Junjie Hu,Zhenpeng Qiu,Qi Wang,Cong Chang,Guohua Zheng,Yan Meng
Selenium nanoparticles (Se NPs) have significant anticancer effects, but their poor water solubility and dispersibility limit their further applications in biomedical fields. Biomacromolecules have often been used as dispersants or stabilizers in synthesized Se NPs because they can enhance the dispersibility of Se NPs and reduce their side effects. Our previous studies reported a triple-helix β-glucan (BFP) from the fruiting bodies of black fungus, which showed a good self-assembly ability in constructing hollow nanotubes for loading metal nanoparticles. Therefore, in the present work, BFP nanotubes were designed as carriers to entrap large amounts of Se NPs in order to enhance their stability and anticancer effects. The results showed that Se NPs were successfully synthesized and loaded inside the BFP nanotubes, and the composite (BFP-Se) exhibited high stability and dispersibility due to the covalent Se–O bonds between the Se NPs and the hydroxyl groups on the BFP nanotubes. Moreover, BFP-Se showed significant effects on the proliferation, apoptosis, and cell cycle of HepG2 cells compared to those exhibited by Se NPs. The mechanism was associated with BFP, which acted as a dispersant or stabilizer, resulting in the enhanced cellular uptake of the Se NPs. BFP also activated the death receptor-mediated and mitochondria-mediated apoptotic pathways in HepG2 cells. These results suggest that BFP-Se has potential applications in biomedical fields, especially for the treatment of human liver cancers.
研究领域:
纳米技术
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生物医学工程
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癌症研究
·
药学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS
·
2020
·Vol. 108
·期 8
·3331-3344
·
IF 2.831
Jiaojun Wei,Dongmei Lei,Maohua Chen,Pan Ran,Xiaohong Li
In vitro cell and tissue models are playing essential roles in the identification of active pharmaceutical ingredients. Though HepG2 cells have attractive profiles over primary hepatocytes in the availability and viability retention, the expression of metabolizing enzymes is quite low. In the current study, three-dimensional (3D) HepG2 spheroids with smaller sizes of 150 μm (3Ds) and bigger sizes of 300 μm (3Db) are engineered using injectable fiber fragments as the substrate. In contrast to two-dimensional (2D) culture, the enzyme activities for drug metabolisms are restored in 3Ds and the pathophysiological profiles of tumor tissues are rebuilt in 3Db spheroids. Compared with spheroid culture without fiber fragments, 3Ds spheroids show higher activities of metabolizing enzymes (CYP3A4, CYP2A9, and phase II) and higher sensitivities to enzyme inducers (rifampicin and glutathione) and inhibitors (ketoconazole and probenecid). The drug clearance and toxicity to 3Ds spheroids predict better the clinical observations and drug–drug interactions. In addition, compared to scaffold-free spheroid culture, stronger expressions of E-cadherin and hypoxia-inducible factor-1α (HIF-1α) and higher fibronectin secretions are determined in 3Db spheroids, displaying apparent hypoxic and apoptotic regions similar to those found in solid tumors. In contrast to the overestimated drug toxicity in other systems, the infiltrations of free drug and drug-loaded micelles are apparently restricted in 3Db spheroids, exhibiting drug resistance just like in tumor tissues. Thus, this study demonstrates HepG2 spheroids with different sizes as predictable and physiologically relevant models for high-throughput screening of drug metabolism and tumor infiltration.
研究领域:
药学
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生物医学工程
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细胞生物学
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组织工程
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2017
·
IF 4.581
Haiyan Sun,Maohua Huang,Nan Yao,Jianyang Hu,Yingjie Li,Liping Chen,Nan Hu,Wencai Ye,William Chi-Shing Tai,Dongmei Zhang,Sibao Chen
Multidrug resistance is the main obstacle in cancer chemotherapy . Emerging evidence demonstrates the important role of autophagy in cancer cell resistance to chemotherapy. Therefore, autophagy inhibition by natural compounds may be a promising strategy for overcoming drug resistance in liver cancer cells. Here, we found that ADCX, a natural cycloartane triterpenoid extracted from the traditional Chinese medicine (TCM) source Cimicifugae rhizoma (Shengma), impaired autophagic degradation by suppressing lysosomal cathepsin B (CTSB) expression in multidrug-resistant liver cancer HepG2/ADM cells, thereby leading to autophagic flux inhibition. Moreover, impairing autophagic flux promoted ADCX-induced apoptotic cell death in HepG2/ADM cells. Interestingly, Akt was overactivated by ADCX treatment, which downregulated CTSB and inhibited autophagic flux. Together, our results provide the first demonstration that an active TCM constituent can overcome multidrug resistance in liver cancer cells via Akt-mediated inhibition of autophagic degradation.
研究领域:
肿瘤学
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药理学
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中药学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
·
2019
·
IF 3.061
Jianying Bai,Zhen He,Yaofu Li,Xuexia Jiang,Hongmei Yu,Qing Tan
Mono-2-ethylhexyl phthalate (MEHP) is a major bioactive metabolite in the widely used industrial plasticizer diethylhexyl phthalate (DEHP) that has been found to be toxic to the liver. The aim of this study is to determine whether MEHP exposure can change the expression of fatty acid metabolism-related genes in HepG2 cells, which might be related to non-alcoholic fatty liver disease (NAFLD). The results revealed that exposure to MEHP promoted lipid accumulation in HepG2 cells. The levels of intracellular triglycerides in the hepatocytes increased after exposure to 0.8–100 μM MEHP for 24 h and 48 h. The genetic expressions of SREBP-1c, ChREBP, ACC1, FASN, and SCD significantly increased at 6 h after exposure to MEHP. At 24 h, the expression of the SREBP-1c and ChREBP genes remained increased, while the expression of the FASN and SCD genes decreased. At 48 h, the expression of SREBP-1c, ChREBP, ACC1, FASN, and SCD decreased. Furthermore, the levels of proteins including ACC1, FASN, SCD, and ChREBP (except SREBP-1c) increased at 24 h. These findings suggest that MEHP exposure can promote fatty acid synthesis in hepatocytes by regulating the expression of relevant genes and proteins, contributing to NAFLD.
研究领域:
毒理学
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细胞生物学
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分子生物学
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肝病学
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2014
·
IF 4.48
Qiang Lv,Meimei Si,Youyou Yan,Fenglei Luo,Guibing Hu,Haoshu Wu,Chongde Sun,Xian Li,Kunsong Chen
Phenolic composition of litchi ( Litchi chinensis Sonn.) pulp from three cultivars was tentatively characterized and quantified by HPLC–MS. Pulp from hemaoli, a wild litchi cultivar, showed the highest content of total phenolics, flavonoids and procyanidins, the latter accounting for the majority of phenolic compounds identified. In hemaoli, (−)-epicatechin was the predominant compound, whereas flavone glycosides accounted for the majority of the phenolic compounds identified in Feizixiao and Lanzhu cultivars, with quercetin rhammosyl-rutinoside being predominant. Hemaoli pulp caused the highest enhancement of glucose consumption rate in HepG2 cells, followed by Feizixiao pulp. This bioactivity was significantly correlated with antioxidant capacity, and total content of phenolics, flavonoids, and procyanidins of different cultivars. (−)-Epicatechin, but not quercetin rhammosyl-rutinoside, also resulted in a significant rise in glucose consumption activity. These results showed that litchi cultivars with high (−)-epicatechin content or high procyanidin content may have great potential as hypoglycaemic foods.
研究领域:
食品科学
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营养学
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药理学
·
植物化学
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产品关联
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2020
·
IF 4.192
Yu Xu,Xiang Li,Wei Gong,Hai-Bo Huang,Bei-Wei Zhu,Jiang-Ning Hu
The aim of this study is to construct a pH- and reduction-responsive nanodrug delivery system to effectively deliver a ginsenoside (Rh2) and enhance its cytotoxicity against human hepatocarcinoma cells (HepG2). Here, pullulan polysaccharide was grafted by urocanic acid and α-lipoic acid (α-LA) to obtain a copolymer, α-LA-conjugated N-urocanyl pullulan (LA-URPA), which was expected to have pH and redox dual response. Then, the copolymer LA-URPA was used to encapsulate ginsenoside Rh2 to form Rh2 nanoparticles (Rh2 NPs). The results showed that Rh2 NPs exhibited an average size of 119.87 nm with a uniform spherical morphology. Of note, Rh2 NPs showed a high encapsulation efficiency of 86.00%. Moreover, Rh2 NPs possessed excellent pH/reduction dual-responsive drug release under acidic conditions (pH 5.5) and glutathione (GSH) stimulation with a low drug leakage of 14.8% within 96 h. Furthermore, Rh2 NPs with pH/reduction dual response had higher cytotoxicity than Rh2 after incubation with HepG2 cells for 72 h, indicating that Rh2 NPs had a longer circulation time. After the treatment with Rh2 NPs, the excessive increase of reactive oxygen species and the decrease of superoxide dismutase, glutathione (GSH), and mitochondrial membrane potential suggested that the mitochondrial pathway mediated by oxidative stress played a role in this Rh2 NP-induced apoptosis. In conclusion, this study provides a new strategy for improving the application of ginsenoside Rh2 in the food and pharmaceutical fields.
研究领域:
药学
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纳米技术
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癌症研究
·
药物递送系统
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2019
·Vol. 20
·期 19
·4803
·
IF 4.183
Shan Jin,Kuan Shi,Liu Liu,Yu Chen,Guangzhong Yang
Xanthones are important chemical constituents ofGarcinia xanthochymusand varied bioactivities including cytotoxicity. However, their anti-tumor mechanism has remained unknown. Here, we isolated and identified a new xanthone named garciniaxanthone I (1) and five known compounds from the bark ofG. xanthochymus. Their structures were elucidated by NMR analysis and HRESIMS. The anti-proliferation activities of all isolated compounds were evaluated on four human tumor cell lines (HepG2, A549, SGC7901, MCF-7). The results demonstrated that the anti-proliferation activity of xanthone was related to the number and location of prenyl groups. We further found that garciniaxanthone I (GXI) could induce HepG2 apoptosis and enhance the expression of cleaved caspase-8, caspase-9, and caspase-3. GXI could also increase Bax level and concurrently reduce the overexpression of Bcl-2, Bcl-XL, Mcl-1, and surviving in HepG2 cells. Moreover, GXI could inhibit cell migration of HepG2 cells by inhibiting the expressions of MMP-7 and MMP-9. In summary, our study suggests that GXI could induce HepG2 apoptosis via the mitochondrial pathway and might become a lead compound for liver cancer treatment.Keywords:xanthones;Garcinia xanthochymus;apoptosis;HepG2;caspase;Bcl-2 family;MMPs
研究领域:
药理学
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肿瘤学
·
细胞生物学
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DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2018
·
IF 3.457
Qingqing Yu,Yayun Liu,Yufei Wu,Yong Chen
Aims Curcumin is a polyphenol compound with many pharmacological activities including antioxidant, lipid-loweing and liver protective. Dihydrocurcumin (DHC) is one of the major metabolites of curcumin. So far, the pharmacological activity of DHC has not been reported. Here, we evaluate the effects of DHC on oleic acid (OA)-induced lipid accumulation, oxidative stress and insulin resistance and the underlying mechanism in L02 and HepG2 cells. Main methods OA-induced L02 and HepG2 cells were used as the in vitro model of nonalcoholic fatty liver disease (NAFLD). Lipid accumulation, oxidative stress, glucose uptake and cell inflammation were evaluated by cellular biochemical assay, respectively. Signaling pathways involved in lipid metabolism including peroxisome proliferator activated receptor-α (PPARα), the sterol regulatory element binding protein-1C (SREBP-1C) and patatin-like phospholipase domain containing 3 (PNPLA3), glucose uptake including phosphatidylinositol 3-kinase (PI3K) and phosphorylated serine-threonine protein kinase (pAKT), and oxidative stress including nuclear factor E2-related factor 2 (Nrf2), cytochrome P450 4A (CYP4A) and 2E1 (CYP2E1) were investigated by western blotting and RT-qPCR, respectively. Key findings DHC decreased the levels of cellular triglycerides (TG) by regulating the mRNA and protein expression levels of SREBP-1C , PNPLA3 and PPARα . At the same time, DHC improved the hepatocellular glucose uptake by increasing the protein expression levels of pAKT and PI3K. Furthermore, DHC reduced the levels of cellular NO and ROS via Nrf2 signaling pathways. Significance The present study firstly revealed that DHC ameliorated OA-induced steatosis through regulating the lipid metabolism, oxidative stress and insulin resistance in HepG2 and L02 cells.
研究领域:
药理学
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细胞生物学
·
代谢
·
肝脏疾病
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产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2015
·Vol. 12
·期 3
·3869-3873
·
IF 1.554
Shi‑Min Yu,Dong‑Hui Hu,Jian‑Jun Zhang
Hepatocellular carcinoma (HCC) is a highly malignant tumor, associated with poor patient prognoses, and high rates of morbidity and mortality. To date, the therapeutic strategies available for the treatment of HCC remain limited. The present study aimed to elucidate the anticancer activity of umbelliferone, a naturally occurring coumarin derivative isolated from Ferula communis, against the HepG2 HCC cell line. A 3‑(4,5‑dimthylthaizol‑2‑yl)‑2,5, diphenyltetrazolium bromide assay was used to evaluate cell viability following umbelliferone treatment, and the effects of umbelliferone on cell cycle progression and apoptosis were evaluated using flow cytometry. The presence of morphological features characteristic of apoptosis, including cell shrinkage, membrane blebbing, nuclear condensation and apoptotic body formation, were evaluated in HepG2 cells following umbelliferone treatment. Cell cycle analysis conducted via propidium iodide (PI) staining indicated that umbelliferone treatment induced cell cycle arrest at S phase in HepG2 cells. Analysis with Annexin V and PI staining revealed that umbelliferone induced apoptotic events in HepG2 cells in a concentration‑dependant manner (0‑50 µM). Umbelliferone also induced dose‑dependant DNA fragmentation. In conclusion, umbelliferone was found to exhibit significant anticancer effects via the induction of apoptosis, cell cycle arrest and DNA fragmentation in HepG2 cancer cells.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2017
·Vol. 7
·期 17
·10108-10117
·
IF 3.108
Shengsheng Zhang,Hai Zhang,Li Wang,Xiaofei Liu,Yuntang Wu
Insulin receptor (InsR) and GLUTs play a very important role in pathophysiological changes in terms of diabetes and insulin resistance, and metformin can regulate their expression and activity in order to alleviate insulin resistance. By reference to the molecular structure of metformin, chitosan biguanidine hydrochloride (CSGH) was synthesized by reacting chitosan (CS) with dicyandiamide under microwave irradiation and characterized by FT-IR, 13C NMR spectroscopy and XRD. The substitution degree (DS) of CSGH, measured by potentiometric titration method, varied in the range of 41.8% to 68.5%. After cytotoxicity testing of CSGH, nontoxic samples were selected. Then insulin resistance (IR) model using human hepatocarcinoma HepG2 cells was established, and the effect of CSGH on glucose consumption was investigated. Moreover, the expression of InsR and the signal protein glucose transporters-2 (GLUT2) were further investigated to study the mechanism. Results showed that CSGH samples with DS 43.2% and DS 52.7% were nontoxic and could improve the vitality, markedly promoting the glucose consumption of HepG2 cells. Besides, the effect of CSGH (DS 52.7%) on promoting glucose consumption was better than metformin and not dose-dependent. It is also found that CSGH could induce the expression of InsR protein and significantly inhibit the over-expression of GLUT2 transport protein, which was probably the mechanism of the therapeutic effect of CSGH on IR HepG2 cells.
研究领域:
药物化学
·
细胞生物学
·
糖尿病研究
✓ 已验证
产品关联
DOI
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 6
·2830
·
IF 4.6
Xiaoyi Feng,Jianchun Li,Hongmei Li,Xuanqin Chen,Dan Liu,Rongtao Li
Euphorbia kansuiis clinically used for the treatment of esophageal cancer, lung cancer, cancerous melanoma, asthma, pleural disorders, ascites, and pertussis, among other conditions. In this study, 12 steroids were obtained and identified fromE. kansui, and cynsaccatol L (5), which showed the best effects in terms of inhibiting the proliferation of HepG2 cells and the immune regulation of macrophages. Furthermore,5induced typical apoptotic characteristics in HepG2 cells, such as morphological changes and the caspase cascade, as well as inducing autophagy-dependent apoptosis via mitochondrial dysfunction and reactive oxygen species (ROS) accumulation. The antitumor mechanism of5might be related to promoting the endocytosis and degradation of ATP1A1 protein and then down-regulating the downstream AKT and ERK signaling pathways. Furthermore, the antiproliferation effect of5in co-cultivation with macrophages was investigated, which showed that5promoted the apoptosis of HepG2 cells by modulating the release of inflammatory cytokines, such as TNF-α and IFN-γ; regulating the M2-subtype polarization of macrophages; promoting the phagocytosis of macrophages. In conclusion,5exerted anti-proliferative effects by promoting the degradation of ATP1A1 and inhibiting the ATP1A1-AKT/ERK signaling pathway in HepG2. Furthermore, it regulated macrophage function in co-cultivation, thereby further exerting adjuvant anti-HepG2 activity.Keywords:Euphorbia kansui;antitumor;immunomodulatory;Na+, K+-ATPase;α1 subunit of NAK;dual antitumor activity
研究领域:
药理学
·
肿瘤学
·
免疫学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2024
·
IF 4.8
Qiuyan Jiang,Tiehua Zhang,Yuan Liang,Jie Zhang
The role of the pregnane X receptor (PXR) extended beyond regulating drug metabolism and transport, it also played a crucial part in lipid metabolism. Baicalein, a flavonoid derived from Scutellaria baicalensis , was demonstrated anti-inflammatory, anti-cancer, and anti-oxidative stress properties. Recent investigations reported its capacity to enhance lipid metabolism disorders. This study aimed to clarify the mechanism via which baicalein exerted its positive effects on lipid metabolism disorders by targeting PXR. The findings indicated that baicalein facilitated the nuclear translocation of PXR and controlled the expression of its target genes. In HepG2 cells with oleic acid and palmitic acid-induced lipid accumulation, baicalein treatment reduced the production of triglycerides, total cholesterol, and lipid droplets. In addition, it decreased the expression of sterol regulatory element-binding protein 1 (SREBP1), as well as lipogenic enzymes fatty acid synthase (FAS) and stearoyl-CoA desaturase-1 (SCD1). The results of computer simulation indicated that baicalein was a natural ligand of PXR. In conclusion, baicalein might potentially alleviate lipid metabolism disorders by targeting the PXR pathway.
研究领域:
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）