RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY
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2022
·Vol. 49
·期 1
·86-100
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IF 1.254
Lingling C.,Hao W.,Fuqiang Y.,Chao G.,Honglin D.,Xiaojie S.,Yang Z.,Jiaxin Z.,Lihong S.,Hongmin L.,Qiurong Z.
Abstract Design and synthesis of two series of trifluoromethyl-containing polysubstituted pyrimidine derivatives in order to seek more effective anti-tumor drugs, and the antiproliferative activity of these compounds against four human tumor cell lines (PC-3, MGC-803, MCF-7, HGC-27) was evaluated by MTT method. Most of the compounds have moderate anti-proliferative activities, among which compounds ( XXId ) and ( XXIe ) have good selectivity for PC-3 cells. The IC 50 (concentration required to achieve 50% inhibition of the tumor cell proliferation) values of compounds ( XXId ) and ( XXIe ) for PC-3 cell were 4.42 ± 0.46 μmol L –1 and 4.85 ± 0.59 μmol L –1 , respectively, and their anti-proliferative activities were significantly better than that of the positive control 5-fluorouracil (6.39 ± 0.71 μmol L –1 ). Molecular docking results indicated that compounds ( XXId ) and ( XXIe ) were likely to be well integrated in the hydrophobic pocket of ubiquitin-specific protease 7 (USP7), which has the value of further research and development.
研究领域:
药物化学
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肿瘤学
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医学
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产品关联
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2019
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IF 3.571
Jinling Cui,Mingzhu Yan,Xiaoyi Liu,Shutao Yin,Shangyun Lu,Lihong Fan,Hongbo Hu
Previous studies have shown that selenite, a representative of inorganic form selenium, exerts its anticancer effect by inducing apoptosis in androgen-dependent LNCaP prostate cancer cells, but few studies have determined the nature of cell death induced by selenite in metastatic androgen-refractory PC-3 cells. Our study showed that necrosis-like cell death rather than apoptosis, pyroptosis, or autophagic cell death was caused by selenite in PC-3 cells. Mechanistically, this type of cell death was caused by ATP depletion (26.28 ± 3.39 nmol/mg of control versus 9.12 ± 2.44 nmol/mg of 10 μM selenite treatment) that resulted from phosphofructokinase activity reduction (100.17 ± 0.17% of control versus 21.74 ± 6.65% of 10 μM selenite treatment). Our study also showed that ROS production is necessary for the decrease in cellular ATP levels and in phosphofructokinase activity. To our knowledge, this is the first study showing that selenite can induce necrosis-like cell death in PC-3 cells. Our findings support selenite as an effective compound for the therapy of apoptosis-resistant prostate cancer.
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
Metabolomics
·
2023
·Vol. 19
·期 2
·1-13
·
IF 3.6
Zhang Rong,Zhang Zijia,Wu Wenyong,Shi Jingying,Berk Entezar,Li Wei,Deng Yanping,Wang Zhaojun,Hou Jinjun,Long Huali,Lei Min,Wu Wanying
Introduction Lipid metabolism participates in various biological processes such as proliferation, apoptosis, migration, invasion, and maintenance of membrane homeostasis of prostate tumor cells. Bufadienolides, the active ingredients of Chansu, show a robust anti-proliferative effect against prostate cancer cells in vitro, but whether bufadienolides could regulate the lipid metabolism in prostate cancer has not been evaluated. Objectives Our study explored the regulatory effects of bufadienolides on lipid metabolism in human prostate carcinoma cells (PC-3). Methods Untargeted lipidomics and transcriptomics were combined to study the effect of different bufadienolides interventions on lipid and gene changes of PC-3 cells. The key genes related to lipid metabolism and prostate cancer development were verified by qPCR and western blotting. Results Lipidomic analysis showed that the active bufadienolides significantly downregulated the content of long-chain lipids of PC-3 cells. Based on transcriptomic and qPCR analyses, many genes related to lipid metabolism were significantly regulated by active bufadienolides, such as ELOVL6 , CYP2E1 , GAL3ST1 , CERS1 , PLA2G10 , PLD1 , SPTLC3, and GPX2 . Bioinformatics analysis of the Cancer Genome Atlas database and literature retrieval showed that elongation of very long-chain fatty acids protein 6 ( ELOVL6 ) and phospholipase D1 ( PLD1 ) might be important regulatory genes. Western blot analysis revealed that active bufadienolides could downregulate PLD1 protein levels which might promote anti-prostate cancer effect. Conclusions All these findings support that bufadienolides might induce lipid metabolic remodeling by regulating long-chain lipids synthesis and phospholipid hydrolysis to achieve an anti-prostate cancer effect, and PLD1 would probably be the key protein.
研究领域:
肿瘤学
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药理学
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分子生物学
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生物化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
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2021
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IF 5.051
Xiang Zhou,Jiamin Liu,Jiao Meng,Yihong Fu,Zhibin Wu,Guiping Ouyang,Zhenchao Wang
Microtubule dynamics are crucial for multiple cell functions, and cancer cells are particularly sensitive to microtubule-modulating agents. Here, we describe the design and synthesis of a series of (Z)-2-(5-benzylidene-4-oxo-2-thioxothiazolidin-3-yl)-N-phenylacetamide derivatives and evaluation of their microtubule-modulating and anticancer activities in vitro. Proliferation assays identified I20 as the most potent of the antiproliferative compounds, with 50% inhibitory concentrations ranging from 7.0 to 20.3 µM with A549, PC-3, and HepG2 human cancer cell lines. Compound I20 also disrupted cancer A549 cell migration in a concentration-dependent manner. Immunofluorescence microscopy, transmission electron microscopy, and tubulin polymerisation assays suggested that compound I20 promoted protofilament assembly. In support of this possibility, computational docking studies revealed a strong interaction between compound I20 and tubulin Arg β369, which is also the binding site for the anticancer drug Taxol. Our results suggest that (Z)-2-(5-benzylidene-4-oxo-2-thioxothiazolidin-3-yl)-N-phenylacetamide derivatives could have utility for the development of microtubule-stabilising therapeutic agents.
研究领域:
肿瘤学
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分子生物学
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药物化学
✓ 已验证
DOI
PubMed
高影响因子
TISSUE & CELL
·
2022
·
IF 2.586
Yaqi Wang,Feng Tian,Yujie Duan,Zhuogang Li,Qiaotong Chen,Jiaying Chen,Xiaomin Miao,Yanhong Xu,Chulan Xu,Yadong Tang
The development of three-dimensional (3D) in vitro model to recapitulate the in vivo tumor tissue is essential for studying tumor biology, discovering anti-cancer drugs, and evaluating anti-cancer drug efficacy . However, most of the previous models lack the involvement of vascular barrier. Here, we proposed an in vitro 3D cocultured tumor-vascular barrier model by the combination of alginate hydrogels beads and Transwell system. PC-3 cells and NIH/3T3 cells were encapsulated in alginate hydrogel beads, which were cultured in the bottom chamber of Transwell, while human umbilical vein endothelial cells (HUVECs) were cultured on the porous membrane in the upper chamber to form vascular barrier. The effect of the concentration of alginate sodium on the morphology, diameter and swelling ratio of the beads was studied. The alginate sodium content and cell seeding density were further optimized according to cell proliferation ability. The formation of endothelial barrier was verified by immunostaining with tight junction protein VE-cadherin and transendothelial electrical resistance (TEER) monitoring. Finally, the drug response of 3D cocultured tumor-vascular barrier model to curcumin was evaluated. Compared with two-dimensional (2D) coculture model and 3D coculture spheroid model, 3D tumor-vascular barrier model showed the highest activity of cancer cells and the strongest drug resistance. The developed 3D cocultured tumor-vascular barrier model possesses great potential to be applied for in vitro evaluation of anti-tumor drugs.
研究领域:
癌症生物学
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药理学
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生物医学工程
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2015
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IF 4.152
Zhiyuan Li,Liu Zhang,Quanshun Li
Herein, N -acetyl- l -leucine-modified polyethylenimine was successfully constructed through the EDC/NHS-mediated coupling reaction and employed as vectors to accomplish p53 gene delivery using HeLa (p53wt) and PC-3 cells (p53null) as models. Compared with PEI25K, the derivatives exhibited lower cytotoxicity, protein adsorption and hemolytic activity, together with satisfactory pDNA condensation capability and gene transfection efficiency. After p53 transfection, MTT analysis confirmed that the cell proliferation was inhibited. Flow cytometric analysis showed that the derivative-mediated p53 delivery could induce stronger early apoptosis than PEI25K and Lipofectamine 2000 . Further, PC-3 cells showed higher sensitivity to the exogenous p53 transfection than HeLa cells. The mechanism for inducing apoptosis was determined to be up-regulation of p53 expression at both mRNA and protein levels using RT-PCR and western blotting analysis. Expression level and activity analysis of caspase-3, -8 and -9, and mitochondrial membrane potential measurement revealed that p53 transfection mediated by these derivatives facilitated early apoptosis of tumor cells via a mitochondria-dependent apoptosis pathway. Thus, the derivatives showed potential as biocompatible carriers for realizing effective tumor gene therapy.
研究领域:
癌症生物学
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分子生物学
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基因治疗
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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