ChemistryOpen
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2024
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IF 2.5
Wei Gao,Xiaoju Hua,Shengliang Liao,Zhikai Xiahou,Haikuan Yang,Lifang Hu,Yunyang Chi
Graphical Compound 3h has been found to show inhibitory effects on the survival of HepG2 liver cancer cells.The results show that 3h induces cell-cycle arrest in the S phase. Additionally, 3h exerts a strong pro-apoptotic effect. Specifically, compound 3h reduces the phosphorylation of PI3K, AKT, and ERK, thereby inhibiting both the MAPK/ERK and PI3K/AKT signaling pathways. 2H-pyran compound 1 synthesized from 6-methylpyridine-2,4-diol and citral, has been used for Cu-catalyzed N -arylation with a range of arylboric acids to obtain arylated pyranopyridine core structure derivatives (yield up to 77 %). Among them, compound 3 h exhibited a much better inhibitory effect on HepG2 liver cancer cells compared to citral, and the IC 50 value was 5.3 μM following exposure with the newly synthesized derivatives (herein named 3 h for short in this paper), which was lower than that of the cisplatin (6.5 μM). Meanwhile, the cell-cycle arrest of HepG2 cells occurred in the S phase, and the apoptosis of HepG2 cells was significantly increased with increasing drug concentration. In addition, real-time fluorescence quantification PCR and Western blotting experiments showed that the expression of apoptotic protein BAX was increased, while the expression of anti-apoptotic protein BCL2 was inhibited in a dose-dependent fashion. The results of these experiments indicated that apoptosis was promoted in HepG2 cells via apoptotic signaling pathway activated by 3 h . Furthermore, 3 h effectively decreased the phosphorylation levels of PI3 K, ATK and ERK, resulting in the inhibitions of MAPK/ERK and PI3 K/ATK signaling pathways. Briefly, 3 h has been found to show inhibitory effects on the survival of HepG2 liver cancer cells and may be used as anti-cancer drug in the future.
研究领域:
药理学
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肿瘤学
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分子生物学
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DOI
PubMed
高影响因子
Journal of Cancer Research and Therapeutics
·
2020
·Vol. 16
·期 2
·209
·
IF 1.326
Yu Haipeng,Zhu Bolan,Yang Wan,Zhang Qian,Wang Wei,Zhai Weichun,Lu Lixia,Zheng Ying,Dang Zheng,Li Bin,Li Chuyi,Liang Bin,Zhang Jiucong,Yu Xiaohui
Objective: To research the effect of matrine on the proliferation and migration of HepG2 cells through extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. Methods: HepG2 cell was selected and divided into blank control group, experimental group ( matrine 1, 2, and 4 mg/mL), and positive control group (PD98059, ERK1/2 inhibitor). MTT measure was used to detect the effective time and concentration which matrine inhibits HepG2 cells. After 24 h, the effect of effective concentration of matrine on the of morphological changing HepG2 cells was observed. The invasion ability was assayed by transwell method, the expression of ERK1/2 and pERK1/2 were detected through Western blot, and reverse transcription polymerase chain reaction was used to test the expression level of ERK1/2 mRNA. Results: With the increase of matrine concentration, the number of adherent HepG2 cells gradually decreased, the morphologic changes gradually became spherical, some cell morphology was incomplete, and even cell fragments appeared. The proliferation and invasion ability of HepG2 cells decreased. The expression of ERK1/2, pERK1/2, and ERK1/2 mRNA downregulated with the increase of matrine concentration (P < 0.05). Conclusion: Matrine inhibits the proliferation and migration of HepG2 cells by downregulating the ERK1/2 signaling pathway.
研究领域:
肿瘤学
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细胞生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
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2017
·Vol. 16
·期 3
·3363-3370
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IF 1.692
Lei Yu,Xin Wang,Zhi‑Feng Chen,Bo Jiang,Dong‑Yu Shang,Yong‑Xue Sun,Jing‑Hui Yang,Lian‑Fang Zhang,Yu‑Bin Ji
Cytisine is a quinolizidine alkaloid, which has been reported to be among the major bioactive components of Sophora alopecuraides L. Quinolizidine alkaloids have previously been demonstrated to inhibit the proliferation of several types of tumor cells. However, few studies have investigated the effects of cytisine on cancer cells. The present study was performed to further investigate the molecular mechanisms underlying cytisine‑induced apoptosis of HepG2 human hepatocellular carcinoma cells. The results of an MTT assay demonstrated that cytisine inhibited the growth of HepG2 cells in a dose‑dependent manner. In addition, the induction of apoptosis was detected, as determined by morphological observation and flow cytometry. As determined by fluorescence microscopy, apoptotic morphological alterations were detected following cytisine administration. Flow cytometric analyses demonstrated that cytisine induced cytotoxicity through apoptosis‑like mechanisms in HepG2 cells. Furthermore, western blot analysis was performed to investigate the release of cytochrome c (Cyt‑c) and activation of the caspase cascade, and the results indicated that treatment of HepG2 cells with cytisine induced caspase‑dependent apoptosis via the release of Cyt‑c from the mitochondria, upregulation of caspase‑3 and downregulation of pro‑caspase‑3. These results indicated that cytisine may induce apoptosis of HepG2 cells through the mitochondrial pathway.
研究领域:
肿瘤学
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细胞生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR PHYSIOLOGY
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2018
·Vol. 234
·期 2
·1880-1888
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IF 3.923
Ying Ye,Yanan Song,Juhua Zhuang,Guoyu Wang,Jing Ni,Wei Xia
Echinacoside (ECH) is a phenylethanoid glycoside extracted from a Chinese herbal medicine, Cistanches salsa . ECH possesses many biological properties, including anti-inflammation, neural protection, liver protection, and antitumor. In the current study, we aimed to explore the effects of ECH on hepatocellular carcinoma (HCC) and the underlying mechanisms. The results showed that ECH could attenuate diethylnitrosamine (DEN)-induced HCC in mice, and exerted antiproliferative and proapoptotic functions on HepG2 HCC cell line. ECH exposure in HepG2 cells dose-dependently reduced the phosphorylation of AKT (p-AKT) and enhanced the expression of p21 (a cell cycle inhibitor) and Bax (a proapoptotic protein). Furthermore, ECH significantly suppressed insulin-like growth factor-1-induced p-AKT and cell proliferation. These data indicated that phosphoinositide 3-kinase (PI3K)/AKT signaling was involved in the anti-HCC activity of ECH. Gene set enrichment analysis results revealed a positive correlation between the PI3K pathway and triggering receptors expressed on myeloid cells 2 (TREM2) expression in HCC tissues. ECH exposure significantly decreased TREM2 protein levels in HepG2 cells and DEN-induced HCC. Furthermore, ECH-mediated proliferation inhibition and AKT signaling inactivation were notably attenuated by TREM2 overexpression. In conclusion, ECH exerted its antitumor activity via decreasing TREM2 expression and PI3K/AKT signaling.
研究领域:
肿瘤学
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药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2014
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IF 2.939
Han-Ming Cui,Qiu-Yan Zhang,Jia-Long Wang,Jian-Long Chen,Yu-Ling Zhang,Xiao-Lin Tong
Ethnopharmacological relevance Berberine (BER) and BER-original herbal medicines have a variety of pharmacological functions and have been widely used in clinical. However, its effect of enzyme induction on cytochrome P450 (CYP) in human hepatocytes is unknown. Material and method Metabolism of berberine and its effect on main metabolic enzymes in HepG2 cell in vitro was investigated. Cocktail probe drugs, mRNA expression and protein expression were used to evaluate the metabolism potency. Meanwhile, an UPLC–MS/MS method was validated for the analysis of BER and four probe drugs in HepG2 cell. Result BER significantly increased the metabolism of midazolam, phenacetin and tolbutamide by inducing the CYP1A2 and 3A4 enzyme in a dose-dependent manner, the mRNA and protein expression of CYP1A2 and 3A4 were increased by berberine at 1000 ng·mL −1 . The activity of CYP1A2 and 3A4 could be induced by BER more than 500 ng·mL −1 in HepG2 cell, which was confirmed by the increase of its mRNA and protein expression. Conclusion BER increases the metabolism of cocktail drugs such as midazolam, phenacetin and tolbutamide by increasing the mRNA and protein expression of CYP1A2 and 3A4.
研究领域:
药理学
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生物化学
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临床医学
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产品关联
DOI
PubMed
高影响因子
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
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2021
·Vol. 105
·期 5
·2033-2042
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IF 4.813
Wang Xiao,Xu Na,Li Qinglin,Chen Shengqi,Cheng Hui,Yang Mo,Jiang Ting,Chu Jun,Ma Xiaojing,Yin Dengke
Liver cancer, one of the most common types of cancer in the world, is the second leading cause of death for cancer patients. For liver cancer, there is an urgent need for an effective treatment with no or less toxic side effects. Lactonic sophorolipids (LSL), as a potential anticancer drug, has attracted wide attention of pharmaceutical researchers with its good biological activities. The effects of LSL and cell death inhibitors were measured by MTT test on HepG2 cells. Meanwhile, the morphology of the cells was observed under a microscope. The apoptosis rate was detected by flow cytometry, and the expression levels of enzyme activity of Caspase-3 and Caspase-9 were measured by detection kits. Meanwhile, mRNA levels of Apaf-1 , Caspase-3 , Bax , and Bcl-2 were measured by quantitative real-time RT-PCR; protein levels of Caspase-3, Cleaved Caspase-3, Bax, and Bcl-2 were measured by western blot. LSL can inhibit the proliferation of cells, and it is possible to induce apoptosis in cells. The HepG2 cells with LSL co-culture exhibited typical apoptotic morphology, and the expression levels of enzyme activity of Caspase-3 and Caspase-9 increased ( P < 0.05). We also found that LSL increases cell apoptosis rate and regulates the expression of genes and proteins associated with apoptosis through the Caspase-3 pathway. These results indicate that LSL may be one of the potential drug candidates to inhibit the proliferation and induce apoptosis in HepG2 cells.
Key points
• LSL, which is of good biological activities such as anti-bacterium, virus elimination, and inflammatory response elimination, has been firstly used to intervene in vitro to investigate its effect on HepG2 cell proliferation. • LSL can inhibit the proliferation of cells, and it is possible to induce apoptosis in HepG2 cells through the Caspase-3 pathway. • The mechanism of LSL action on HepG2 cell proliferation was firstly also discussed, which provides a certain experimental reference for the clinical treatment of liver cancer. Graphical abstract
研究领域:
肿瘤学
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药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2020
·
IF 3.69
Li-Juan Zhao,Hai-Yu Zhao,Xiao-Lu Wei,Fei-Fei Guo,Jun-Ying Wei,Hong-Jie Wang,Jian Yang,Zhi-Gang Yang,Nan Si,Bao-Lin Bian
Ethnopharmacological relevance Arenobufagin (ArBu) is an important anti-tumor ingredient of Chan'su which has long been used as traditional Chinese medicine in clinic for tumor therapy in China. Aim of the study The purpose of our study is to investigate the lipid homeostasis regulation effects of ArBu on zebrafish model of liver cancer and hepatoma cells, and to provide a reference for further clarifying its active mechanisms. Materials and methods The zebrafish xenograft model was established by injecting HepG2 cells stained with CM-Dil red fluorescent dye . Both the xenograft model and HepG2 cells were used to evaluate the anti-hepatoma activity of ArBu. High performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was the main method to study lipidomics, proteomics and the semiquantification of endogenous metabolites. Bioinformatics was used as an assistant tool to further explore the antitumor mechanism of ArBu. Results The lipidomics analysis revealed that ArBu caused differential lipids changes in a dose-dependent manner, including PCs, PEs, TGs, SMs, DGs, Cer and PA . PCs, PEs, SMs and TGs were markedly altered in both two models. The influence of glycerophospholipid metabolism was the major and commonly affected pathway. Notably, DGs and Cer were significantly changed only in HepG2 cells. Furthermore, the proteomics research in HepG2 cells fished the target proteins related to lipid homeostasis abnormalities and tumor suppression. ArBu reduced the expression of 65 differential proteins associated with the lipid metabolism, apoptosis and autophagy, such as LCLAT1, STAT3, TSPO and RPS27. Meanwhile, 7 amino acids of 29 determined metabolites were significantly changed, including tyrosine, glutamate , glutamine, leucine , threonine , arginine and isoleucine . Conclusion ArBu has a significant anti-hepatoma effect in vitro and a therapeutic effect on zebrafish xenograft model. It regulated the lipid homeostasis. Activated SM synthase and arginine deiminase , inhibited sphingomyelinase , amino acid supply and JAK-STAT3 signaling pathway, and the affected glycerophospholipid metabolism might explain these results.
研究领域:
药理学
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肿瘤学
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生物化学
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分子生物学
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民族药理学
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产品关联
DOI
PubMed
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
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2020
·
IF 2.365
Wen Yuan,Meixing Yan,Yitong Wang,Xia Liu,Yanling Gong
This study was aimed at evaluating the potential of peach gum (PG) and gelatin in the microencapsulation of eugenol and the intervention of eugenol microcapsules on hepatic steatosis in vitro. Response surface method (RSM) was used to optimize the encapsulation conditions of eugenol microcapsules. The microcapsules were characterized by scanning electron microscopy (SEM), dynamic Light Scattering (DLS), Fourier transform infrared spectroscopy (FT-IR) and release behavior in vitro was determined. The effect of eugenol microcapsules on free fatty acids (FFA) treated hepatocellular cells (HepG2) cells was evaluated by oil red O staining and intracellular total cholesterol (TC) and triglyceride (TG) determination. The results showed that the optimal encapsulation conditions were as follows: the PG-gelatin ratio was 1.6:1.4, the core-wall ratio was 1.6:1.4, the pH was 4 and the emulsification speed was 9000 r/min. The optimized microcapsules were smooth spherical with a size of about 3.09 ± 0.58 μm and the encapsulation was confirmed by FT-IR. In vitro release behavior showed that eugenol microcapsules could be released stably in a neutral environment for 72 h. Oil red O staining showed that 50 and 100 μM eugenol microcapsules could significantly inhibit the lipid accumulation and reduce the TC and TG in steatotic HepG2 cells induced by FFA. Therefore, PG and gelatin can be used as excellent carriers for the microencapsulation of volatile compounds in the field of biomedical industry, and eugenol microcapsules is a promising preparation for the treatment of nonalcoholic fatty liver disease (NAFLD).
研究领域:
药理学
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生物医学工程
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肝脏疾病研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CEREAL SCIENCE
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2019
·
IF 2.452
Feier Cheng,Xinhui Ge,Caifeng Gao,Yunlong Li,Min Wang
Epidemiological studies have shown that D-chiro-inositol (DCI) has multiple health effects in humans. Buckwheat , a nutritional staple crop, is a dietary source of DCI. We established a new economic method to accurately detect DCI content in buckwheat samples and investigated the antioxidant effect of DCI. In this study, we analyzed the content and form of DCI in buckwheat with different varieties, growth stages, and milled parts of seeds using pre-column derivatization and high performance liquid chromatography-ultraviolet detection. The total DCI content of ZK-2 and DT-1 was the highest. During buckwheat growth, DCI content was the highest in mature leaves. DCI was mainly in bound form in flowers and grains and mainly in free form in roots and stems. The highest content of DCI was 60–100-mesh in size in buckwheat grains. The results of cell experiments showed that DCI can inhibit the oxidative stress of HepG2 cells induced by palmitic acid (PA). This study will assist in the processing and utilization of buckwheat and provide an important basis for the scientific and effective use of D-chiro-inositol resources to increase the maximization of buckwheat resources.
研究领域:
营养学
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生物化学
·
药理学
·
农业科学
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产品关联
DOI
高影响因子
Journal of Functional Foods
·
2023
·
IF 5.6
Shuqi He,Zhiyuan Xu,Jie Li,Yueping Guo,Qianxia Lin,Huoxi Jin
Three oligopeptides of KLHDEEVA (KA-8), LALFVPR (LR-7), and PSRILYG (PG-7) were selected from the hydrolysate of Harpadon nehereus . They significantly improved cell morphology and decreased aspartate aminotransferase (AST), alanine transaminase (ALT), and reactive oxygen species (ROS) levels in high glucose-induced HepG2 cells. LR-7 showed good performance in regulating both antioxidant and glucose metabolism in high glucose-induced HepG2 cells, evidenced by improved expression levels of glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase 1 (PEPCK1), heme-oxygenase (HO-1), NAD(P)H: quinone oxidoreductase 1 (NQO1), and nuclear factor E2-related factor 2 (Nrf2). PG-7 had better performance in reducing triglyceride (TG) and total cholesterol (TC) levels and enhancing superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity levels. KA-8 showed stronger effects on improving low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), phosphorylation protein kinase B (p-AKT), and phosphorylation glycogen synthase kinase-3 (p-GSK-3β) levels. The results showed that all three peptides could protect against high glucose-induced HepG2 damage through different molecular mechanisms. The protective effects of LR-7 may be attributed mainly to its excellent glycolipid metabolism regulation and oxidative stress attenuation via Nrf2 pathway activation. KA-8 may exert its protective role through AKT/GSK-3β signaling pathway activation.
研究领域:
生物化学
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分子生物学
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医学
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DOI
高影响因子
Oncology Letters
·
2017
·Vol. 15
·期 3
·2881-2888
·
IF 1.39
Xiaoning Liu,Jingjing Kang,Hui Wang,Tao Huang
Oridonin, the main active constituent of Rabdosia rubescens, is known to exert antitumor activity via the induction of apoptosis in numerous types of human cancer cells. However, the underlying regulatory mechanisms of mitochondrial ROS in oridonin‑induced HepG2 apoptosis remain largely unknown, due to limitations of subcellular imaging resolution. Previously, it has been suggested that mitochondria serve a potential role in sensing and signaling cellular redox changes in vital biological processes such as cell death and the abiotic stress response, based on studies involving the mitochondrial‑targeted redox‑sensitive green fluorescent protein (GFP). To address this, a mitochondrial‑targeted Grx1‑roGFP2 (mtGrx1‑roGFP2) biosensor was implemented to monitor real‑time mitochondrial redox changes of HepG2 cells in response to either H2O2/DTT or oridonin/SS31 treatment. It was determined that oridonin caused a perturbation in mitochondrial redox status, which in turn contributed to oridonin‑induced apoptosis. Furthermore, a novel mechanism underlying the regulation of mitochondrial redox changes in oridonin‑induced HepG2 apoptosis, presumably dependent on PARP cleavage, was proposed. In conclusion, the present study provides evidence in support of mitochondrial redox changes as a potential mediator in the apoptotic activities of oridonin in HepG2 cells, which provides insight into the molecular mechanisms by which mitochondrial redox signaling regulates oridonin‑induced apoptosis in cancer therapy, and the development of mitochondria‑specific oridonin as a promising novel anticancer therapeutic strategy.
研究领域:
癌症生物学
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细胞信号传导
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2021
·
IF 6.558
Kai Nan,Man He,Beibei Chen,Bin Hu
For a deep understanding of arsenic's mutagenicity , carcinogenicity and teratogenicity , the elucidation of arsenic binding proteins in organisms is a necessary prerequisite. Herein, a biotinylated phenylarsenite (Bio-PAO(III)) probe was synthesized for in situ binding to arsenic binding proteins in HepG2 cells. The Bio-PAO(III)-arsenic binding proteins complexes were captured by the prepared streptavidin-magnetic beads (SA-MBs) by specific interaction of biotin-SA. After magnetic separation, the arsenic binding proteins in the eluent was separated by sodium dodecyl sulfate-polyacrylamide - gel electrophoresis , and the in-gel tryptic digested protein bands were subjected to capillary high performance liquid chromatography coupled with electrospray ionization mass spectrometry analysis. 32 kinds of arsenic binding proteins were identified in HepG2 cells, which could be divided into three groups, structure proteins, enzymes related with tricarboxylic acid cycle and fatty synthesis and transcriptional regulator. Poly [ADP-ribose] polymerase 1 and general transcription factor IIH subunit 1 were identified to bind with arsenicals, which may affect the process of nucleotide excision repair in HepG2 cells.
研究领域:
毒理学
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蛋白质组学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）