Frontiers in Pharmacology
·
2023
·
IF 5.6
Qi Lai,Chun-Ju Yang,Qi zhang,Min Zhuang,Yan-Hua Ma,Cheng-Yuan Lin,Guang-Zhi Zeng,Jun-Lin Yin
Liver cancer belongs to Gastrointestinal (GI) malignancies which is a common clinical disease, a thorny public health problem, and one of the major diseases that endanger human health. Molecules from natural products (NPs) or their derivatives play an increasingly important role in various chronic diseases such as GI cancers. The chemical composition of the Alstonia yunnanensis Diels roots was studied using silica column chromatography, gel chromatography, recrystallization, and HPLC, and the compounds were structurally identified by modern spectral analysis using mass spectrometry (MS) and nuclear magnetic resonance ( 1 H-, 13 C-, HMQC-, HMBC-, and 1 H- 1 HCOSY-NMR), ultraviolet and visible spectrum (UV), and electronic Circular Dichroism (ECD). Acetoxytabernosine (AC), an indole alkaloid with antitumor activity, was isolated from Alstonia yunnanensis Diels root. The current study aimed to investigate the influence of AC on the cell proliferation of BEL-7402 and SMMC7721 and to elucidate the underlying mechanism. The absolute configuration of AC was calculated by ECD (electronic circular dichroism). The effects of AC on the viability of different tumor cell lines were studied by the SRB method. The death mode of human hepatoma cells caused by AC was studied by TUNEL cell apoptosis detection and AnnexinV-FITC/PI double staining image. Mitochondrial membrane potential was detected by JC-1. The effects of AC on the expression of apoptosis-related proteins (Caspase9, Caspase3, and Parp-1) in SMMC7721 and BEL-7402 cells were detected by western blot. It was found that the absolute configuration of AC is 19(s), 20(s)-Acetoxytabernosine. AC could induce apoptosis of SMMC7721 and BEL-7402, and block the replication of DNA in the G1 phase. Under the treatment of AC, the total protein expression of apoptosis-related proteins (Caspase9, Caspase3, and Parp-1) significantly decreased in SMMC7721 and BEL-7402. The results suggested that AC induced apoptosis through a caspase-dependent intrinsic pathway in SMMC7721 and BEL-7402, and natural product-based drug development is an important direction in antitumor drug discovery and research.
研究领域:
药理学
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肿瘤学
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天然产物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Toxins
·
2025
·Vol. 17
·期 9
·426
·
IF 4
Jie Wang,Wangzhuo Fu,Xuezhen Ma,Lin Chen,Weitao Song,Sumei Ling,Hongyun Qian,Shihua Wang,Zhenhong Zhuang
Due to the severe hazard of aflatoxins (AFs) to humans, it is of great significance to detect the key aflatoxins, aflatoxin B1(AFB1) and aflatoxin G1(AFG1), in food and feed in simple, rapid, and semi-quantitative ways. The hybridoma clone 3A1 was prepared in this study, and anti-AFB1monoclonal antibody (mAb) with high specificity and affinity (9.38 × 108L/mol) from 3A1 was purified. The indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) demonstrated that the linear detection range for AFB1was 0.029–1.526 ng/mL with a limits of determination (LOD) of 0.023 ng/mL. A latex microsphere-based immunochromatographic test strip (LM-ICTS) was constructed based on 3A1, which showed that the strip could detect AFB1(LOD: lower than 1.79 ng/mL) and AFG1(LOD: lower than 8.08 ng/mL), and the linear detection ranges for AFB1and AFG1are 1.79–48.46 ng/mL and 8.08–107.40 ng/mL, respectively. The average recoveries of intra-assay and inter-assay for peanuts were (98.4 ± 4.7)% and (92.6 ± 7.6)%, and the average coefficient of variation (CVs) were 4.38% and 8.15%, respectively. For sunflower seeds, the intra-assay and inter-assay recoveries were (94.4 ± 7.2)% and (89.2 ± 4.3)%, and the average CVs were 6.6% and 4.9%, respectively. In summary, the developed LM-ICTS exhibited excellent sensitivity and specificity, which provided a rapidly stable on-site detection choice for AFB1and AFG1to contaminated agricultural samples, including grain and feed.
研究领域:
免疫学
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食品安全
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分析化学
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分子生物学
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农产品质量检测
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毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Nutrition Research
·
2021
·
IF 3.894
Mengling Zhang,Jian Liu,Rui Zhang,Zengenni Liang,Shenghua Ding,Huanling Yu,Yang Shan
Background Hypoxia is associated with abnormal cell apoptosis in trophoblast cells, which causes fetal growth restriction and related placental pathologies. Few effective methods for the prevention and treatment of placenta-related diseases exist. Natural products and functional foods have always been a rich source of potential anti-apoptotic drugs. Nobiletin (NOB), a hexamethoxyflavonoid derived from the citrus pomace, shows an anti-apoptotic activity, which is a non-toxic constituent of dietary phytochemicals approved by the Food and Drug Administration. However, their effects on hypoxia-induced human trophoblast cells have not been fully studied. Objective The aim of this study was to investigate the protective effects of NOB on hypoxia-induced apoptosis of human trophoblast JEG-3 and BeWo cells, and their underlying mechanisms. Design First, the protective effect of NOB on hypoxia-induced apoptosis of JEG-3 and BeWo cells was studied. Cell viability and membrane integrity were determined by CCK-8 assay and lactate dehydrogenase activity, respectively. Real Time Quantitative PCR (RT-qPCR) and Western blot analysis were used to detect the mRNA and protein levels of HIF1α. Propidium iodide (PI)-labeled flow cytometry was used to detect cell cycle distribution. Cell apoptosis was detected by flow cytometry with Annexin V-FITC and PI double staining, and the expression of apoptosis marker protein cl-PARP was detected by Western blot analysis. Then, the molecular mechanism of NOB against apoptosis was investigated. Computer molecular docking and dynamics were used to simulate the interaction between NOB and p53 protein, and this interaction was verified in vitro by Ultraviolet and visible spectrum (UV-visible spectroscopy), fluorescence spectroscopy and circular dichroism. Furthermore, the changes in the expression of p53 signaling pathway genes and proteins were detected by RT-qPCR and Western blot analysis, respectively. Results Hypoxia treatment resulted in a decreased cell viability and cell membrane integrity in JEG-3 and BeWo cell lines, and an increased expression of HIF1α, cell cycle arrest in the G1 phase, and massive cell apoptosis, which were alleviated after NOB treatment. Molecular docking and dynamics simulations found that NOB spontaneously bonded to human p53 protein, leading to the change of protein conformation. The intermolecular interaction between NOB and human p53 protein was further confirmed by UV-visible spectroscopy, fluorescence spectroscopy and circular dichroism. After the treatment of 100 μM NOB, a down-regulation of mRNA and protein levels of p53 and p21 and an up-regulation of BCL2/BAX mRNA and protein ratio were observed in JEG-3 cells; however, there was also a down-regulation of mRNA and protein levels observed for p53 and p21 in BeWo cells after the treatment of NOB. The BCL2/BAX ratio of BeWo cells did not change after the treatment of 100 μM NOB. Conclusion NOB attenuated hypoxia-induced apoptosis in JEG-3 and BeWo cell lines and might be a potential functional ingredient to prevent pregnancy-related diseases caused by hypoxia-induced apoptosis. These findings would also suggest the exploration and utilization of citrus resources, and the development of citrus industry.
研究领域:
药理学
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细胞生物学
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分子生物学
·
妇产科学
✓ 已验证
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2024
·
IF 2.7
Xiong-Li Liu,Shuang Chen,Xi-Rui Wang,Wei-Na Wang,Ke-Lan Xu,Pan Hu,Ying Zhou,Bo-Wen Pan,Qi-Lin Wang
Here, we demonstrate that the first example of harmaline scaffolds serving as acceptor/acceptor-based N-C-C synthons-triggered the ring opening and skeletal reconstruction of 3-vinyl benzofuranones for the construction of a library of skeletally-diverse polycyclic harmaline scaffolds. These products were smoothly afforded in up to 77% yield, >20:1 dr under catalyst-free conditions, and expanded the chemical space of biologically significant harmaline derivative species. All synthetic compounds showed cytotoxic activity against tumor cells, especially the compound 3at, which exhibited selective cytotoxicity against A549 cells and lower cytotoxicity against normal cells MRC-5 and HK-2. In further mechanism research, 3at inhibited A549 cell proliferation through the G1 phase arrest, induced A549 cell apoptosis through internal and external apoptosis pathways, and suppressed the migration and invasion abilities of A549 cells. These data indicated that compound 3at is the most effective compound in the series and can serve as a promising precursor for drug development.
研究领域:
药物化学
·
肿瘤学
·
药学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Kemin Mao,Xianghong Wang,Yakun Hou,Xiaowei He,Shuo Geng,Faizan Ahmed Sadiq,Yunhe Lian,Yaxin Sang
Equol is an isoflavone-derived metabolite known to exhibit strong estrogenic and antioxidant activities. The aim of this paper is twofold: first, to confirm the anticancer potential of equol against colorectal cancer, and second, to reveal the underlying mechanisms. After treatment with 40 μg/mL equol, cell proliferation, cell migration, and colony formation of HCT116 colon cancer cells were inhibited. Network pharmacology and transcriptomics analysis revealed the downregulation of genes related to DNA replication (CCND1, E2F1, CDC6, CDC45, MCM4), leading to G1/S cell cycle arrest and the induction of cell apoptosis, which was confirmed by flow cytometry. Genes associated with the G2-to-M transition (CDK1, CCNA2, CCNB1) were also downregulated. In addition, equol downregulated genes (FOXM1 and ASPM) that control cell migration and invasion. Our data indicate that equol can inhibit colorectal cancer by targeting multiple pathways, suggesting its potential as a key component in the adjuvant treatment of colorectal cancer.
研究领域:
药理学
·
肿瘤学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
APOPTOSIS
·
2018
·Vol. 23
·期 2
·132-142
·
IF 3.967
Hu Cuihua,Chen Xiaolong,Huang Yibing,Chen Yuxin
In this study, a peptide–peptide co-administration therapy between hybrid peptide kla-TAT and cationic anticancer peptide HPRP-A1 was designed to increase the anticancer activity of the combination peptides through synergistic effect. kla is a pro-apoptotic peptide which could induce rapid cancer cell apoptosis by disruption the mitochondrial membrane when internalized the cells. To enhance more kla peptides pass through cell membrane, a double improvement strategy was designed by chemically conjugation with cell penetration peptide TAT as well as co-administration with cationic membrane active peptide HPRP-A1, and the double anticancer mechanism of the kla-TAT peptide and HPRP-A1 including membrane disruption and apoptosis induction was verified through in vitro experiments. The CompuSyn synergism/antagonism analysis showed that kla-TAT acted synergistically with HPRP-A1 against a non-small cell lung cancer (NSCLC) A549 cell line. The anticancer activities of the two peptides were dramatically increased by co-administration, under the mechanism of cell membrane disruption, caspase-dependent apoptosis induction, as well as cyclin-D1 down-regulation based G1 phase arrest. We believe that the synergic therapeutic strategy would be a meaningful method for the anticancer peptides used in cancer treatment.
研究领域:
肿瘤学
·
药学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2017
·Vol. 7
·期 1
·1-13
·
IF 4.259
Hu Dongfang,Cao Shengliang,Zhang Guihua,Xiao Yihong,Liu Sidang,Shang Yingli
Florfenicol (FLO) is one of the most popular antibiotics used in veterinary clinic and aquaculture. FLO can inhibit both bacterial and mitochondrial protein synthesis. However, the effects of FLO on mitochondrial function and cellular homeostasis remain unclear. Here we show that FLO inhibits expression of mitochondrial DNA-encoded proteins, decreases mitochondrial membrane potential, and promotes generation of reactive oxygen species (ROS) in vitro . As a result, activities of mitochondrial respiratory chain complex I and IV and the cellular ATP level are decreased and mitochondrial morphology is damaged. FLO represses cell growth and proliferation by suppression of phosphorylation of p70S6K through AMPK/mTOR/p70S6K pathway. Furthermore, FLO also induces G0/G1 cell cycle arrest via increase of p21 levels through activating ROS/p53/p21 pathway. Moreover, the clearance of damaged mitochondria by autophagy is impaired, leading to cell proliferation inhibition and promotes cell senescence. In addition, FLO-induced upregulation of cytosolic p53 may contribute to mitophagy deficiency via regulation of Parkin recruitment. In summary, our data suggest that florfenicol is an inhibitor of mitochondrial protein synthesis that can induce noticeable cytotoxicity. Thus, these findings can be useful for guiding the proper use of FLO and the development of safe drugs.
研究领域:
兽医学
·
细胞生物学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Inorganic Chemistry Frontiers
·
2019
·Vol. 6
·期 4
·1040-1049
·
IF 5.934
Yi-Gang Wu,Dong-Bo Wang,Juan-Juan Hu,Xue-Qing Song,Cheng-Zhi Xie,Zhong-Ying Ma,Jing-Yuan Xu
The design, synthesis, crystal structures and in vitro biological assessment of three iron(III) complexes, namely [Fe(L1)2]Cl (1), [Fe(L2)2]·FeCl4 (2) and [Fe(L3)(HL3)2]·(FeCl4)2·(CH3OH) (3) (HL1 = N’-(4-oxothiazolidin-2-ylidene)picolinohydrazonamide, HL2 = 2-(2-(1-(pyridin-2-yl)ethylidene)hydrazono)thiazolidin-4-one, HL3 = 3-ethyl-2-(2-(1-(pyridin-2-yl)ethylidene)hydrazono)thiazolidin-4-one, are reported in this article. Single crystal X-ray diffraction revealed that all three complexes were mononuclear molecules, approaching a coordination polyhedron of octahedral geometry, in which the 4-thiazolidinone derivative ligands exhibited different coordination modes and conformations. Their interactions with DNA were investigated by UV–visible and fluorescence spectrometries, and by agarose gel electrophoresis. Results indicated that they presented efficient DNA binding propensities and cleavage activities. In vitro, the iron(III) complexes caused cell cycle arrest at the G1 phase in response to DNA damage, effectively inhibited the cyclinD1 expression and decreased the migration of HeLa cells with a lower wound-healing rate than that of the control. Complex 3 was the most sensitive to HeLa cancer cells, followed by 2 and 1. Attractively, the tested complexes demonstrated significantly enhanced selectivity index values determined for HeLa vs. LO2 normal cells compared with cisplatin, especially for complex 3, which was up to 13.94-fold. Unlike cisplatin, more complex 3 would accumulate in HeLa cancer cells compared with LO2 normal cells.
研究领域:
无机化学
·
药物化学
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肿瘤学
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分子生物学
·
生物化学
✓ 已验证
产品关联
DOI
高影响因子
Small
·
2016
·Vol. 12
·期 19
·2595-2608
·
IF 8.315
Yu Gao,Songen Gu,Yingying Zhang,Xiaodong Xie,Ting Yu,Yusheng Lu,Yewei Zhu,Wenge Chen,Huijuan Zhang,Haiyan Dong,Patrick J. Sinko,Lee Jia
The circulating tumor cells (CTCs) existing in cancer survivors are considered the root cause of cancer metastasis. To prevent the devastating metastasis cascade from initiation, we hypothesize that a biodegradable nanomaterial loaded with the abortifacient mifepristone (MIF) and conjugated with the epithelial cell adhesion molecule antibody (aEpCAM) may serve as a safe and effective cancer metastatic preventive agent by targeting CTCs and preventing their adhesion-invasion to vascular intima. It is demonstrated that MIF-loaded mesoporous silica nanoparticles (MSN) coated with aEpCAM (aE-MSN-M) can specifically target and bind colorectal cancer cells in either cell medium or blood through EpCAM recognition proven by quantitative flow cytometric detection and free aEpCAM competitive assay. The specific binding results in downregulation of the captured cells and drives them into G0/G1 phase primarily attributed to the effect of aEpCAM. The functional nanoparticles significantly inhibit the heteroadhesion between cancer cells and endothelial cells, suggesting the combined inhibition effects of aEpCAM and MIF on E-selectin and ICAM-1 expression. The functionalized nanoparticles circulate in mouse blood long enough to deliver MIF and inhibit lung metastasis. The present proof-of-concept study shows that the aE-MSN-M can prevent cancer metastasis by restraining CTC activity and their adhesion-invasion to vascular intima.
研究领域:
纳米技术
·
癌症生物学
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR NUTRITION & FOOD RESEARCH
·
2023
·
IF 5.2
Da Huang,Pei-En Wu,Zi-Jie Chen,Yan-Chun Pang,Zi-Wei Xu,Jingbo Tan,Zhi-Hua Jiang,Bing-Bing Yang,Ruoting Zhan,Hui Xu,Yong-Qiang Liu
Scope This study aims to investigate the anticancer properties of Citrus grandis ‘Tomentosa’ (CGT) in non-small cell lung cancer (NSCLC). Methods and results The ethanol extract of CGT (CGTE) is prepared by using anhydrous ethanol and analyzed by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), revealing that the main chemical components in CGTE are flavonoids and coumarins, such as naringin, rhoifolin, apigenin, bergaptol, and osthole. CGTE at concentrations without inducing cell death significantly inhibits cell proliferation via inducing cell cycle G1 phase arrest by MTT, colony formation, and flow cytometry assays, implying that CGT has anticancer potential. CGTE markedly inhibits the activity of Skp2-SCF E3 ubiquitin ligase, decreases the protein level of Skp2, and promotes the accumulation of p27 by co-immunoprecipitation (co-IP) and in vivo ubiquitination assay; whereas Skp2 overexpression rescues the effects of CGTE in NSCLC cells. In subcutaneous LLC allograft and A549 xenograft mouse models, CGTE, without causing obvious side effects in mice, significantly inhibits lung tumor growth by targeting the Skp2/p27 signaling pathway. Conclusion These findings demonstrate that CGTE efficiently inhibits NSCLC proliferation both in vitro and in vivo by targeting the Skp2/p27 signaling pathway, suggesting that CGTE may serve as a therapeutic candidate for NSCLC treatment.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Yanrui Chen,Xingran Zhang,Fang Li,Jinxing Ma,Zhiwei Wang
Biofouling remains to be one of major obstacles for membrane-based technology in water and wastewater treatment, calling for the development of antibiofouling membranes. For the traditional release-killing strategy, uncontrollable release of biocides and thus a short lifetime as well as the potentially environmental risk are thorny issues for the modified membranes. Herein, hydrophilic hydrogel multilayers with controllable thickness at nanometer scale on a poly(vinylidene fluoride) (PVDF) microfiltration membrane were constructed via layer-by-layer (LbL) self-assembly of non-drug-resistant antimicrobial peptides (AMPs) and alginate . The AMPs/alginate multilayers modified membranes exhibited enhanced hydrophilicity, well-controlled pore size distribution and prominent antimicrobial ability against Escherichia coli and Staphylococcus aureus . As the number of multilayers of alginate increased, both initial and steady release rate of Ponericin G1 reduced; in particular, the AMPs/alginate modified membranes with fifteen multilayers (MSA 15 ) had the slowest release kinetics ( i.e., an initial release rate of 1.79 ± 0.07 μg/cm 2 d and a steady release rate of 0.55 ± 0.03 μg/cm 2 d), resulting in about 60% less release compared with the AMPs/alginate modified membranes with five multilayers (MSA 5 ). Long-term antibiofouling tests showed that the AMPs/alginate modified membranes with ten multilayers (MSA 10 ) exhibited a significantly reduced transmembrane pressure increase rate of 0.81 ± 0.01 kPa/d which was much lower than that of the control membranes (1.80 ± 0.20 kPa/d), mainly attributed to the antibacterial activity imparted by the lasting release of AMPs and competing membrane basic properties. Furthermore, the AMPs/alginate multilayers modified membranes revealed high stability suffering from long-term operation and chemical cleaning cycles. The novel AMP/alginate-incorporated modifying method provides a new dimension to enhance antibiofouling performance of membranes for water and wastewater treatment.
研究领域:
环境工程
·
材料科学
·
水处理
·
膜技术
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF SEPARATION SCIENCE
·
2016
·Vol. 39
·期 19
·3789-3797
·
IF 2.741
Jiao Zhao,Yan Zhu,Yang Jiao,Jinyan Ning,Yaling Yang
A novel two-step extraction technique combining ionic-liquid-based dispersive liquid–liquid microextraction with magnetic solid-phase extraction was developed for the preconcentration and separation of aflatoxins in animal feedstuffs before high-performance liquid chromatography coupled with fluorescence detection. In this work, ionic liquid 1-octyl-3-methylimidazolium hexafluorophosphate was used as the extractant in dispersive liquid–liquid microextraction, and hydrophobic pelargonic acid modified Fe 3 O 4 magnetic nanoparticles as an efficient adsorbent were applied to retrieve the aflatoxins-containing ionic liquid. Notably, the target of magnetic nanoparticles was the ionic liquid rather than the aflatoxins. Because of the rapid mass transfer associated with the dispersive liquid–liquid microextraction and magnetic solid phase steps, fast extraction could be achieved. The main parameters affecting the extraction recoveries of aflatoxins were investigated and optimized. Under the optimum conditions, vortexing at 2500 rpm for 1 min in the dispersive liquid–liquid microextraction and magnetic solid-phase extraction and then desorption by sonication for 2 min with acetonitrile as eluent. The recoveries were 90.3–103.7% with relative standard deviations of 3.2–6.4%. Good linearity was observed with correlation coefficients ranged from 0.9986 to 0.9995. The detection limits were 0.632, 0.087, 0.422 and 0.146 ng/mL for aflatoxins B 1 , B2, G1, and G2, respectively. The results were also compared with the pretreatment method carried out by conventional immunoaffinity columns.
研究领域:
分析化学
·
食品安全
·
环境科学
✓ 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）