MEDICINAL CHEMISTRY RESEARCH
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2021
·Vol. 30
·期 6
·1240-1248
·
IF 1.965
Shi Bo-Ya,Wang Ze-Hao,Zhang Ning,Xie Yin-Rong,Sun Xiu-Li,Yang Hao-Nan,Wu Yi-Long,Zi Cheng-Ting,Wang Xuan-Jun,Sheng Jun
Novel glucosylated (-)-epigallocatechin-3-gallate derivatives 10 – 13 having the EGCG analogs conjugated to the d -glucosyl azide were synthesized by carrying out the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction, and were evaluated for their cytotoxicities against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW480) using MTT assays. Compounds 10 and 11 showed the highest levels of cytotoxicity against the HL-60 cells with IC 50 values of 4.57 and 3.78 μM, respectively, and showed moderate selectivity toward cancer cell lines. Compound 11 was also shown to induce apoptosis in HL-60 cells. Most notably, inclusion of the perbutyrylated glucose residue in an EGCG derivative was concluded to lead to increased anticancer activity.
研究领域:
药物化学
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肿瘤学
·
有机合成
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产品关联
DOI
高影响因子
ARCHIVES OF PHARMACAL RESEARCH
·
2015
·Vol. 39
·期 2
·172-177
·
IF 2.046
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.
研究领域:
药理学
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植物化学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2019
·Vol. 34
·期 5
·666-673
·
IF 2.649
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.
研究领域:
毒理学
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免疫学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Analytical Cellular Pathology
·
2023
·
IF 3.2
Fan Du,Ting Jin,Li Wang
Objective. Acute myeloid leukemia (AML) is a heterogeneous malignancy with a low long-term survival rate. The aim of this study was to investigate the effects of decitabine (DAC) treatment cell proliferation and apoptosis in AML and role of the expression of LINC00599 and, consequently, miR-135a-5p. Materials and Methods. Human promyelocytic leukemia cells (HL-60) and human acute lymphatic leukemia (CCRF-CEM) cells were treated with various concentrations of DAC. Cell proliferation in each group was detected using the cell counting kit 8. For each group, apoptosis and reactive oxygen species (ROS) levels were detected using flow cytometry. Reverse transcription polymerase chain reaction (RT-PCR) was performed to examine the expression of lncRNA LINC00599. The expression of apoptosis-related proteins was analyzed using western blotting. The regulatory relationship between miR-135a-5p and LINC00599 was verified by constructing miR-135a-5p mimics, miR-135a-5p inhibit, wild type LINC00599 3-untranslated region (UTR), and mutant LINC00599 3-UTR. Ki-67 expression in the tumor tissues of nude mice was detected using immunofluorescent assays. Results. Both DAC and LINC00599 Inhibit groups were able to significantly reduce the proliferation of HL60 and CCRF-CEM cells, increase apoptosis, upregulate the expression of Bad, cleaved caspase-3, and miR-135a-5p, downregulate the expression of Bcl-2, and elevate ROS levels in cells, with these effects being more pronounced after combined treatment with DAC and LINC00599 Inhibit. In comparison to mimic NC, the miR-135a-5p mimic group significantly decreased the relative fluorescence activity ratio of LINC00599 3-UTR wild-type CCRF-CEM cells. The LINC00599 Inhibit and miR-135a-5p mimic groups exhibited substantially reduced proliferation of HL60 and CCRF-CEM cells, increased apoptosis, upregulated Bad, cleaved caspase-3, and miR-135a-5p expression, along with downregulated Bcl-2 and LINC00599 expression and increased ROS levels in cells; these effects were more pronounced after LINC00599 Inhibit was combined with miR-135a-5p mimics. In vivo experiments revealed that both DAC and LINC00599 Inhibit were able to considerably reduce the long diameter, short meridian, volume, and mass of tumors, increase miR-135a-5p expression, and decrease LINC00599 and ki-67 expression in tumor tissues of nude mice. This effect was more pronounced when the DAC and LINC00599 Inhibit were used in combination. Conclusion. DAC regulates the expression of miR-135a-5p by regulating the expression of LINC00599, which in turn affects cell proliferation, apoptosis, and tumor proliferation. Our findings provide a theoretical basis for improving the clinical outcome of AML.
研究领域:
肿瘤学
·
血液学
·
分子生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2016
·
IF 7.476
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.
研究领域:
分析化学
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医学
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生物化学
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产品关联
DOI
PubMed
高影响因子
Anti-Cancer Agents in Medicinal Chemistry
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2013
·Vol. 13
·期 8
·1280-1290
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IF 2.61
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
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生物化学
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肿瘤学
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细胞生物学
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天然产物化学
✓ 已验证
DOI
高影响因子
Frontiers in Pharmacology
·
2025
·
IF 4.8
Donghan Bai,Zihao Zhang,Jingyue Gao,Qiaochu Wang,Remy Macdonald,Ziwen Xu,Shumin Chen,Nanxi Huang,Lu Luo
Background: Leukemia is a malignant hematologic disease that poses a serious threat to human health. Realgar-Indigo Naturalis formula (RIF), a traditional Chinese medicine formula, have demonstrated anti-tumor activity, but its mechanisms of action remain unclear.Objective: This study aimed to establish a zebrafish HL-60 tumor transplantation model to investigate the anti-leukemic effects of RIF and explore its underlying mechanisms.Methods: The zebrafish HL-60 tumor transplantation model was established, with RIF as the intervention drug and all-trans retinoic acid (ATRA) as the control. Anti-tumor efficacy was assessed via pharmacodynamic analysis. Transcriptomic analysis further elucidated gene expression profiles, differentially expressed genes, and relevant biological pathways.Results: RIF significantly reduced tumor cell fluorescence intensity, demonstrating anti-tumor efficacy. Additionally, it improved HL-60-induced liver damage in zebrafish, as evidenced by a reduction in fatty vacuolar degeneration in liver tissue. Transcriptomic analysis revealed that ATRA mainly affected the FoxO signaling pathway, PI3K-Akt signaling pathway, apoptosis, and complement and coagulation cascades in leukemia treatment. RIF primarily influenced the ubiquitin-proteasome system, ferroptosis, and glutathione metabolism. The combination of ATRA and RIF also affected autophagosome and lysosome pathways, in addition to the aforementioned pathways.Conclusion: RIF exhibit significant anti-tumor effects through modulation of multiple pathways. This study provides a theoretical foundation for the potential clinical application of RIF in leukemia treatment.
研究领域:
肿瘤学
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药理学
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中医学
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发育生物学
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毒理学
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基因组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2022
·
IF 5.364
Boyang Cheng,Xindang Chu,Ruiwen Liu,Xinyuan Ma,Mengyang Wang,Jiayi Zhang,Pingxuan Jiao,Qianqian Gao,Wenxiao Ma,Yongmin Zhang,Chuanke Zhao,Demin Zhou,Sulong Xiao
Betulinic acid (BA) and oleanolic acid (OA) are plant-derived conjugates found in various medicinal plants that have emerged as potential antitumor agents. Herein, a series of novel BA and OA derivatives were synthesized by conjugation with per-O-methylated-β-cyclodextrin (PM-β-CD), and their anticancer properties against a panel of three human cancer cell lines were evaluated. Two OA-PM-β-CD conjugates (48 and 50) were observed to be the most potent conjugates against the three cell lines (MCF-7, BGC-823, and HL-60), with a 15- to 20-fold decrease in the IC50 values (IC50: 6.06–8.47 μM) compared with their parental conjugate (OA). Annexin V-FITC/propidium iodide staining and Western blot analysis revealed that both conjugates induced apoptosis in HL-60 cells. Additionally, in the representative conjugate 48-treated HL-60 cells, a decrease in mitochondrial membrane potential and subsequent release of cytochrome c into the cytosol were observed, indicating the activation of the intrinsic apoptosis pathway. Furthermore, 48 dramatically induced the generation of reactive oxygen species (ROS) in HL-60 cells, and the corresponding effect could be reversed using the ROS scavenger N-acetylcysteine. Collectively, these results suggest that the novel pentacyclic triterpenoid derivatives trigger the intrinsic apoptotic pathways via the ROS-mediated activation of caspase-3 signaling, inducing cell death in human cancer cells.
研究领域:
药理学
·
肿瘤学
·
药物化学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Chinese Medicine
·
2025
·Vol. 20
·期 1
·1-18
·
IF 5.7
Wang Xu,Peng Hui-Ming,Zhang Meng-Ru,Li Jing-Jing,Zhao Chuan-Peng,Zhang Ya-Li,Wang Si-Yu,Zhu Si-Ying,Lu Jian-Kang,Yin Hai-Long,Yin Qiang,Fang Jin-Bo
Background Steroid-resistant asthma (SRA) is a form of asthma resistant to corticosteroid therapy, which is characterized by the presence of neutrophil-predominant inflammatory response and neutrophil extracellular traps (NETs) formation. Hyssopus cuspidatus Boriss., a traditional Uyghur medicine, is known for its efficacy in treating inflammatory lung conditions such as asthma. However, the therapeutic impact and underlying mechanisms of Hyssopus cuspidatus Boriss.’s volatile oil (HVO) in SRA have not been fully elucidated. Methods This study established an ovalbumin/lipopolysaccharide (OVA/LPS)-induced SRA mice model to evaluate the therapeutic effect of HVO on SRA. UPLC-QE-Orbitrap-MS was applied to analyze the serum compositions of HVO. Network pharmacology and molecular docking were employed to uncover the complex mechanisms of HVO in treating SRA and predict potential effective compounds in HVO. Furthermore, in vivo studies in SRA mice and in vitro studies using HL-60 cells and bone marrow neutrophils were conducted to validate the mechanism. Results HVO could significantly ameliorate OVA/LPS-induced SRA symptoms, including airway hyperresponsiveness, airway inflammation, mucus overproduction and airway remodeling. 41 prototype compounds, 65 Phase I metabolites and 50 Phase II metabolites were identified in serum-containing HVO. The integration of network pharmacology with experimental validation revealed that HVO can inhibit the formation of NETs by targeting neutrophil elastase, thereby exerting a therapeutic influence on SRA. Meanwhile, molecular docking results showed that 3-methoxy-4-hydroxy mandelonitrile, 1,2,3,4-tetrahydro-1,5,7-trimethyl-naphthalene, cis-calamenene and aristol-1(10)-en-9-yl isovalerate may be the therapeutic compounds of HVO in treating SRA. Conclusion These findings suggest that HVO is a promising therapeutic candidate for neutrophil-dominant SRA by targeting NETs formation.
研究领域:
药理学
·
免疫学
·
呼吸病学
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传统医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）