RSC Medicinal Chemistry
·
2026
·
IF 4.6
Shi-Ying Xu,Quan-Xing Liu,Yan Luo,Wu-He Wu,Qing Li,Shang-Gao Liao,Jun-Li Ao,Guo-Bo Xu
The broad biological activity of synthetic halogenated steroid derivatives has spurred considerable recent research. In this study, we synthesized and evaluated cytotoxicity against HepG2 cells for twenty-eight halogen-containing pregnenolone derivatives. Compound 20 exhibited the highest cytotoxicity, with an IC50 value of 1.490 ± 0.041 μM. It effectively inhibited cell proliferation, clone formation, and migration, as well as induced DNA damage in hepatocellular carcinoma cells. Flow cytometry revealed that compound 20 induced G0/G1 cell cycle arrest. Concurrently, experimental evidence from Hoechst 33258 staining, flow cytometry, and western blotting convincingly demonstrated that compound 20 robustly promotes apoptosis in HepG2 cells, marked by decreased expression of pro-survival proteins (caspase 3/8/9, Bcl-2) and increased expression of pro-apoptotic Bax. Network pharmacology identified PPARγ as a key potential target. Western blots using a PPARγ agonist (pioglitazone) and antagonist (T0070907) validated its crucial role in mediating compound 20-induced apoptosis in HepG2 cells. Complementary molecular modeling, including docking and molecular dynamics simulations, underscored the high binding affinity and stabilizing interaction between compound 20 and PPARγ. Furthermore, a CETSA assay provided additional support, confirming that compound 20 enhances PPARγ's thermal stability. Collectively, these findings strongly suggest that compound 20 inhibits HepG2 proliferation and promotes HepG2 apoptosis via PPARγ modulation, positioning it as a promising lead compound for hepatocellular carcinoma treatment.
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高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2025
·Vol. 26
·期 22
·11216
·
IF 4.9
Bin Wang,Meng-Yun Wang,Yu-Pei Yang,Wei Su,Xin Jiang,Shi-Qi Liu,Qu-Jing Luo,Wen-Chao Zhou,Ling Liang,Hao Zheng,Qing-Ling Xie,Huang-He Yu,Yu-Qing Jian,Xu-Dong Zhou,Bin Li,Cai-Yun Peng,Wei Wang
Clematis henryi(C. henryi) is a valuable medicinal plant in the Tujia ethnic family, which is widely used for the treatment of rheumatism arthritis and limb numbness. There are few studies on the chemical composition and biological activity ofC. henryiat present. In this study, we isolated and purified thirty-one compounds in total, including four new compounds (1,29–31) and twenty-seven known compounds (2–28). These isolated compounds were identified by a variety of spectroscopic data including NMR spectrometry and mass spectroscopy. These thirty-one compounds were tested for their proliferation inhibition activity on RAFLs and HepG2 cells. The results indicated that compound29and30exhibited weak inhibition of proliferation activity against RAFLs cells. Meanwhile, compounds8,10,29, and30exhibited moderate inhibition of proliferation activity on HepG2 cells with an IC50value between 16.07 and 19.83 µM. The results of this study could serve as a reference for the further comprehensive utilization ofC. henryi.
研究领域:
植物化学
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药理学
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民族植物学
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癌症研究
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天然产物化学
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高影响因子
MICROCHEMICAL JOURNAL
·
2024
·
IF 4.9
Yongqiang Wang,Xingyu Hou,Yali Li,Xue Sun,Rui Hu,Yuguang Lv,Rui Jia,Lixin Ding
Luteolin (3′,4′,5,7-tetrahydroxyflavone, LTL) is a kind of hydrophobic flavonoid, which has a number of pharmacological actions. It has a number of pharmacological actions, including anti-inflammatory, antioxidant, anticancer, and antihepatic fibrosis properties. High-dose LTL, on the other hand, can cause oxidative DNA damage and hydroxyl radical generation. It is critical to create easy, sensitive, and dependable LTL detection technologies and delivery methods for LTL quality control, clinical drug monitoring and enhancing drug bioavailability. In this work, a novel phenylboronic acid derived quantum dots (P-QDs) were synthesized for LTL sensitive detection and pH-responsive delivery. It showed remarkable selectivity and a brilliant fluorescence with a quantum yield of 43.62 %. In vitro experiments reveal negligible cytotoxicity. P-QDs and LTL coupling (P-QDs/LTL) showed powerful proliferation inhibition and migration restriction effects on HepG2 cells. In addition, P-QDs/LTL could time-dependently release it to restore fluorescence in the microacidic environment of HepG2 cells, thus demonstrating satisfactory fluorescence imaging capability. This strategy demonstrated a favourable linear relationship between LTL concentration and the fluorescence intensity of P-QDs in the range of 0.02–200 μM ( R 2 = 0.9952), with a detection limit of 1.16 nM (S/N=3). The recoveries in different real samples were in the range of 85.23 %-108.04 % with RSDs ≤6.1 %. The material is both a new attempt at LTL detection methodology and has significant promise for providing pH-responsive intracellular release of drug monitoring and cancer therapies from naked QDs without the requirement for sophisticated modified grafting.
研究领域:
药理学
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生物医学工程
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分析化学
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DOI
高影响因子
MOLECULES
·
2019
·Vol. 24
·期 7
·1211
·
IF 3.06
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
研究领域:
材料科学
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毒理学
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生物医学工程
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高影响因子
MICROCHIMICA ACTA
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2019
·Vol. 186
·期 2
·1-9
·
IF 5.479
Zheng Jiushang,Wang Bin,Jin Yanzi,Weng Bo,Chen Jiucun
A novel MXene-based biomimetic enzyme was synthesized using adenosine triphosphate (ATP) as a template to modify a Mn 3 (PO 4 ) 2 nanostructure on Mxene-Ti 3 C 2 nanosheets. The resulting composite was used as an electrode material in an electrochemical sensor for superoxide anion (O 2 •− ). It displays excellent catalytic properties which is attributed to the synergistic effects of the two-dimensional conductive substrate and the Mn 3 (PO 4 ) 2 nanoparticles. The addition of ATP results in the formation of a porous and ordered nanostructure of Mn 3 (PO 4 ) 2 . This facilitates the electron transfer between O 2 •− and electrode. The sensor, best operated at 0.75 V (vs. Ag/AgCl), displays a rapid amperometric response with a detection limit of 0.5 nM and an analytical range that extends from 2.5 nM to 14 μM. Conceivably, it has potential in the detection of O 2 •− released by living cells.
Nanostructured MXenes were synthesized by in-situ growth of Mn 3 (PO 4 ) 2 on Ti 3 C 2 nanosheets under the induction of adenosine triphosphate (ATP). They display enzyme mimickong properties. A sensor fabricated with the composites can be used for the detection of superoxide anions released by HepG2 cells.
研究领域:
材料科学
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电化学
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生物传感器
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纳米技术
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高影响因子
Food & Function
·
2021
·Vol. 12
·期 23
·12115-12126
·
IF 5.396
Lele Yang,Jiliang Cao,Jinchao Wei,Jiagang Deng,Xiaotao Hou,Erwei Hao,Zhengcai Du,Liang Zou,Peng Li
The therapeutic targets of berberine for hepatocellular carcinoma (HCC) and its detailed mechanisms remain unexplored. Here, an integration of network pharmacology, proteomic, bioinformatic and in vitro biochemical approach was proposed to reveal therapeutic targets and pathways underlying the antiproliferative activity of berberine against HepG2 cells. Results indicated that berberine caused the cytotoxicity and inhibited the growth of HepG2 cells with IC50 values ranging from 92 μM to 118 μM. Network pharmacology analysis revealed that targeting apoptosis and cell cycle pathways by berberine contributed to its antitumor efficacy against HCC. Proteomic analysis demonstrated that mitochondria-related apoptosis pathways were involved in the cytotoxic action of berberine, as evidenced by the expression of mitochondrial dysfunction-mediated proteins. Moreover, a total of 160 significantly altered proteins were screened, among which AKAP12 presented significantly increased levels under berberine treatment. Bioinformatic analysis of various public datasets showed that expression of AKAP12 in HCC liver tissues was downregulated, emphasizing its role as a tumor suppressor. Immunoblotting validated the increased levels of AKAP12, while co-immunoprecipitation identified its interaction with Cyclin D1. These data, together with flow cytometry analysis, suggested that AKAP12 mediated cell cycle arrest, thereby suppressing cell proliferation. Altogether, the antiproliferative action of berberine in HepG2 cells involves both apoptosis and cell cycle arrest. Regulating AKAP12 signalling by berberine might provide a promising strategy for HCC treatment.
研究领域:
肿瘤学
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药理学
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生物信息学
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细胞生物学
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DOI
PubMed
高影响因子
Scientific Reports
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2026
·
IF 4.9
Liu Wenjing,Cong He,Wang Xin,Jiao Yawen,Meng Rui,Liu Shan,Zhang Kaijin
The distinct conditions of the marine habitat drive microorganisms to synthesize exopolysaccharides possessing unique structural features and a broad spectrum of bioactive properties. An extracellular polysaccharide (AVP1) was obtained from the fermented liquid of a marine Aspergillus versicolor CS13 from the Yellow River Delta sediment. AVP1 was characterized as a mannogalactan with a molecular weight of approximately 16.2 kDa and a mannose-to-galactose molar ratio of 1.0: 2.4. The polysaccharide AVP1 was constituted by a backbone of →2)-α- d -Man p -(1→ and →5)-β- d -Gal f -(1→ units, and branch at C-6 of →5)-β- d -Gal f -(1→ units. The side chains contained →6)-α- d -Man p -(1→ and α- d -Man p -(1→ units. AVP1 possessed an obvious α‑amylase inhibitory activity in vitro. AVP1 significantly enhanced insulin sensitivity and glucose consumption in insulin-resistant (IR)-HepG2 cells, and alleviated sodium palmitate (PA)-induced insulin resistance. Moreover, AVP1 effectively reduced total cholesterol (TC) and triglyceride (TG) levels, while increased the activities of superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH). It also decreased malondialdehyde (MDA) content and reactive oxygen species (ROS) levels, thereby improved lipid metabolism and mitigated oxidative stress in IR-HepG2 cells. These results demonstrated that AVP1 exhibited notable restorative effects in IR-HepG2 cells and possessed strong activity to alleviate insulin resistance in vitro. This study provides a basis for the development of novel marine-derived hypoglycemic agents.
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高影响因子
ANALYTICAL CHEMISTRY
·
2018
·
IF 6.042
Zhichao Liu,Shengnan Wang,Wanying Li,Yang Tian
Iron ions, as a main component of intracellular labile iron, not only play an important function in oxygen transport, enzymatic reactions, and electron transport but also are vitally important in oxidative stress. In this work, we developed a ratiometric fluorescent biosensor for ferrous ion (Fe2+), in which gold nanoclusters (AuNCs) were synthesized as a stable fluorescent probe and a ligand (FeL) was designed for specific recognition of Fe2+ and conjugated onto AuNCs (AuNC@FeL). Meanwhile, water-soluble sulfocyanine 7 N-hydroxysuccinimide ester (Cy7 NHS ester) was immobilized onto AuNC@FeL as a reference element. The developed ratiometric fluorescent nansosensor displayed good linearity with the concentration of Fe2+ in the range of 1–105 μM, and detection limit was achieved down to 210 nM. In addition, this nanosensor responded to Fe2+ in less than 1.23 s and showed high selectivity against other metal ions, amino acids, and reactive oxygen species. With the advantages of high selectivity and accuracy, as well as quick response and long-term stability, this organic–inorganic ratiometric fluorescent probe was successfully applied in real-time biosensing and bioimaging of Fe2+ in neurons and HepG2 cells. By use of this tool, it was found that the increasing concentration of Fe2+ in live cells was closely related to oxidative stress.
研究领域:
生物成像
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细胞生物学
·
分析化学
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PubMed
高影响因子
CHEMOSPHERE
·
2019
·
IF 5.108
Tao Huang,Ying Huang,Yu Huang,Yi Yang,Yuanhui Zhao,Christopher J. Martyniuk
Acetochlor is a high-volume herbicide used on a global scale and toxicity assessments are needed to define its potential for adverse effects in wildlife and humans. This study was conducted to determine the effects of acetochlor on human liver carcinoma cells (HepG2), a cell model widely used to assess the potential for chemical hepatotoxicity. Experiments were conducted at concentrations ranging 0–800 μM acetochlor over a 12 to 48h period to quantify underlying mechanisms of toxicity. Our data indicate that acetochlor suppressed HepG2 cell proliferation in both a concentration- and time-dependent manner. Acetochlor induced reactive oxygen species (ROS) generation more than 700% with exposure to 400 μM acetochlor, and acetochlor decreased the activities and levels of anti-oxidant responses (superoxide dismutase, glutathione) following exposure to 100 μM, 200 μM and 400 μM acetochlor. Acetochlor also (1) induced HepG2 cell damage through apoptotic-signaling pathways; (2) enhanced intracellular free Ca 2+ concentration (>400%); (3) decreased mitochondrial transmembrane potential (∼77%), and reduced ATP levels (∼65%) following exposure to 400 μM acetochlor compared to untreated cells. Notably, cell cycle progression was blocked at G0/G1 phase in HepG2 cells when treated for 24 h with 400 μM acetochlor. Taken together, acetochlor induced significant cytotoxicity toward HepG2 cells, and the underlying toxicity mechanisms appear to be related to ROS generation, mitochondrial dysfunction and disruption in the cell cycle regulation. These data contribute to toxicity assessments for acetochlor, a high-use herbicide, to quantify risk to wildlife and human health.
研究领域:
毒理学
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环境科学
·
细胞生物学
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PubMed
高影响因子
CELLULAR SIGNALLING
·
2025
·
IF 3.7
JingjingLi,Juan Gu,SijiaPan,Nuo Deng,Muhammad Khan,Lingyan Li,Xiao Wu,Yongming Li
Despite continuous therapeutic interventions, the prognosis of hepatocellular carcinoma (HCC) remains very poor. Thus, quest for novel treatment strategies to improve therapeutic window of HCC therapy is paramount. Arsenic trioxide (ATO) is commonly used as the first-line treatment for acute promyelocytic leukemia (APL). Isoliquiritigenin (ISL) is a potential plant-based bioactive molecule with versatile biological and pharmacological effects including anticancer effect. The present study aimed to investigate the potential synergistic effects of combination of ISL and ATO in HCC cells. The data revealed that the combination of ISL and ATO synergistically inhibited HCC cell proliferation. The collective data demonstrate that synergistic anticancer effect of combined treatment of ISL + ATO was achieved via cooperative induction of mitochondrial apoptosis through ROS generation and inhibition of PI3K/Akt/mTOR pathway. In addition, ROS generation and suppression of PI3K/Akt/mTOR pathway were found to be two independent events in induction of apoptosis. Finally, we observed that combination treatment effectively suppressed tumor growth in nude mice xenograft model through induction of intrinsic apoptosis and inhibition of PI3K/Akt/mTOR pathway. In conclusion, the findings of this study suggest that both drugs work synergistically to exert anti-tumor effect in HCC, both in-vitro and in-vivo and could offer novel strategy for liver cancer treatment.
研究领域:
肿瘤学
·
药理学
·
分子生物学
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PubMed
高影响因子
CHEMOSPHERE
·
2017
·
IF 4.208
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
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PubMed
高影响因子
CHEMICAL PAPERS
·
2026
·
IF 2.7
Weng Xuling,Guo Fang,Zhong Yu,Feng Wanyun,Shang Xiaoqiang,Chen Yufeng
A drug delivery system based on magadiite for gemcitabine (namely GEM-Mag) has been constructed by protonation, intercalation with tetrabutylammonium ions (TBA + ), and ion exchange. Various measurements were used to characterize the samples. XRD results showed that the basal spacing of Na-magadiite (15.17 Å) decreased to 11.40 Å after protonation. Following intercalation with TBA + , the basal spacing increased to 25.79 Å. After further ion exchange with the positively charged GEM, the basal spacing reduced to 18.21 Å. FT-IR and TG-DTG indicated that the GEM was incorporated into the magadiite. Based on CHN elemental analysis and EDS results, the chemical formula of GEM-Mag was estimated to be H 1.59 (C 9 H 12 F 2 N 3 O 4 ) 0.41 Si 14 O 29 ·2.33H 2 O. According to the chemical formula, the loading capacity of GEM-Mag for GEM was 10.74%. Drug release tests were carried out either in phosphate buffered solution (PBS, pH = 7.40) or in HCl solution (pH = 1.35). Results revealed that the GEM-Mag exhibited sustained-release of GEM. While the drug released for 96 h in the PBS, the cumulative release percentage of GEM from drug delivery system was only 53.46%; whereas in the HCl solution (pH = 1.35), the cumulative release percentage was 52.15% after 700 min. Cytotoxicity assay confirmed that the magadiite-based drug delivery system for GEM exhibited stronger inhibitory effects on HepG2 cells compared with that of the free GEM. In addition, the drug-loading process and mechanisms have been discussed in detail.
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高影响因子
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