JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2019
·
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
·
药理学
✓ 已验证
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
·
药理学
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分子生物学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2015
·
IF 3.574
Dongli Li,Zhiyun Du,Chenyue Li,Yue Liu,Susan Goodin,Huarong Huang,Yan He,Yuan Zhang,Huaqian Wang,Xi Zheng,Kun Zhang
Five terpenoids ( 1 – 5 ) from a vegetable plant Acanthopanax trifoliatus (L.) Merr. were investigated for their effects on human prostate cancer cells. The diterpenoid ( 3 ) and triterpenoids ( 4 and 5 ) were found to inhibit the growth and stimulate apoptosis in PC-3 cells. The effects of these terpenoids on PC-3 cells were associated with strong suppression of nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3). These terpenoids also inhibited the expression of survivin, a downstream target of NF-κB and STAT3. The in vivo study using a xenograft mouse model showed that 5 strongly inhibited the formation and growth of PC-3 tumours. Moreover, treatment with 5 strongly decreased the expression of phospho-STAT3 and survivin in PC-3 tumours. Our results indicate that 5 has preventive efficacy on the development of PC-3 xenograft tumours. This terpenoid may serve as a candidate for future development as a novel agent for prostate cancer prevention.
研究领域:
肿瘤学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY
·
2022
·Vol. 49
·期 1
·86-100
·
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
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF BIOCHEMISTRY
·
2024
·
IF 2.1
Wang Rui,Liao Zhaoping,Liu Chunhua,Yu Shifang,Xiang Kaihua,Wu Ting,Feng Jie,Ding Senjuan,Yu Tingao,Cheng Gang,Li Sanlian
Prostate cancer (PCa) has become a worldwide health burden among men. Previous studies have suggested that Cellular Retinoic Acid Binding Protein 2 (CRABP2) significantly affects the regulation of cell proliferation, motility, and apoptosis in multiple cancers, yet the effect of CRABP2 on PCa is poorly reported. The CRABP2 expression in different PCa cell lines and its effect on different cellular functions were various. While CRABP2 promotes cell migration and invasion, it appears to inhibit cell proliferation specifically in PC-3 cells. However, the proliferation of DU145 and 22RV1 cells did not appear to be significantly affected by CRABP2. Besides, CRABP2 had no influence on the cell cycle distribution of PCa cells. RNA-seq assay showed that overexpressing CRABP2 up-regulated Laminin subunit beta-3 (LAMB3) mRNA expression, and the enrichment analyses revealed that the differentially expressed genes were enriched in PI3K/AKT and MAPK signaling pathway. The following WB experiments also confirmed the up-regulated LAMB3 protein level and the activation of PI3K/AKT and MAPK signaling pathways. Moreover, overexpressing CRABP2 inhibited tumor growth significantly in vivo. In conclusion, CRABP2 facilitates cell migration and invasion by activating PI3K/AKT and MAPK signaling pathways through upregulating LAMB3 in PCa.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
✓ 已验证
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2013
·
IF 5.008
Qiao An,Chuanyu Sun,Dian Li,Ke Xu,Jia Guo,Changchun Wang
Ascorbic acid (AA) is capable of inhibiting cancer cell growth by perturbing the normal redox state of cells and causing toxic effects through the generation of abundant reactive-oxygen species (ROS). However, the clinical utility of AA at a tolerable dosage is plagued by a relatively low in vivo efficacy. This study describes the development of a peroxidase-like composite nanoparticle for use in an AA-mediated therapeutic strategy. On the basis of a high-throughput, one-pot solvothermal approach, Fe3O4@C nanoparticles (NPs) were synthesized and then modified with folic acid (FA) on the surface. Particular focus is concentrated on the assessment of peroxidase-like catalytic activity by a chromogenic reaction in the presence of H2O2. The carbon shell of Fe3O4@C NPs contains partially graphitized carbon and thus facilitates electron transfer in the catalytic decomposition of H2O2, leading to the production of highly reactive hydroxyl radicals. Along with magnetic responsiveness and receptor-binding specificity, the intrinsic peroxidase-like catalytic activity of Fe3O4@C-FA NPs pronouncedly promotes AA-induced oxidative stress in cancer cells and optimizes the ROS-mediated antineoplastic efficacy of exogenous AA. In vitro experiments using human prostate cancer PC-3 cells demonstrate that Fe3O4@C-FA NPs serve as a peroxidase mimic to create hydroxyl radicals from endogenous H2O2 that is yielded in response to exogenous AA via an oxidative stress process. The usage of a dual agent leads to the enhanced cytotoxicity of PC-3 cells, and, because of the synergistic effect of NPs, the administrated dosage of AA is reduced markedly. However, because normal cells (HEK 293T cells) appear to have a higher capacity to cope with additionally generated ROS than cancer cells, the NP–AA combination shows little damage in this case, proving that selective killing of cancer cells could be achieved owing to preferential accumulation of ROS in cancer cells. A possible ROS-mediated mechanism is discussed to elucidate the pharmaceutical profile of the NP–AA agent. In general, this foundational study reveals that the peroxidase-like nanomaterials are applicable for modulating oxidative stress for the selective treatment of cancer cells by generating a high level of endogenous ROS.
研究领域:
纳米医学
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肿瘤学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2019
·Vol. 34
·期 4
·817-824
·
IF 3.766
Mingming Zhu,Xi Yu,Zongmei Zheng,Jiaming Huang,Xuepan Yang,Hongfei Shi
Cancer stem cells (CSCs) are considered as the origin and driving cells of cancer, and play a key role in the progress of cancer. Studies have shown that capsaicin exerted inhibitory effect on prostate cancer cells, however, the effects of capsaicin on prostate CSCs remain undefined. In the present study, we showed that capsaicin could downregulate prostate CSCs markers and inhibit the growth of PC-3 and DU145 prostate cancer stem cells. Further, we found capsaicin suppressed the expression of Wnt-2, p-GSK3β and β-catenin, along with downregulation of Wnt/β-catenin pathway target genes c-myc and cyclinD1. Using LiCl, a activator of Wnt/β-catenin pathway, we found activation of Wnt/β-catenin pathway could ameliorate the downregulation of prostate CSCs markers and the growth inhibition induced by capsaicin in prostate cancer stem cells. Those data suggested that the inhibition effect of capsaicin on prostate cancer stem cells and the anti-cancer effect of capsaicin on prostate cancer stem cell may be mediated by Wnt/β-catenin pathway. Findings from this study reveals for the first time the potential role and mechanisms of capsaicin on prostate cancer stem cells.
研究领域:
肿瘤学
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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
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
·
2021
·
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
·
分子生物学
·
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
·
药理学
·
生物医学工程
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 92
·89484-89491
·
IF 3.289
Yingshuai Liu,Jin Xie,Zeying Zhang,Zhisong Lu
O-GlcNAcylation is a very important post-translational modification of nucleocytoplasmic proteins. Aberrant O-GlcNacylation has been found in a variety of human diseases including many types of cancers, diabetes, and Alzheimer's disease. However, analysis of protein O-GlcNacylation still remains a great challenge due to its low levels and labile nature. Herein, a highly sensitive and reliable colorimetric method is developed by use of wheat germ agglutinin (WGA) lectin for specific recognition of O-GlcNAc and gold nanoparticle (AuNP)-catalyzed copper deposition for signal amplification. In presence of the target molecule, AuNP is specifically introduced onto the sensing surface and then catalyzes the copper deposition. An Au@Cu core–shell structure is produced from the deposition. The obtained copper shell on AuNP is dissolved by FeCl3 due to the oxidation–reduction reaction between copper and Fe3+, resulting in Cu2+ and Fe2+, which subsequently form a red coordination complex in the presence of bathophenanthrolinedisulfonic acid disodium salt (BPT2−). Thus, the amount of the red complex is proportional to the level of O-GlcNAc. Qualitative O-GlcNAc detection is realized by direct readout with the naked eye, while the quantitative analysis is achieved by measurement of the absorbance using a UV-Vis spectrophotometer. With increasing time, more and more copper is deposited on the surface of AuNP, thus achieving significant signal amplification. Under optimal conditions, an ultralow limit of detection (LOD) down to 0.02 pg mL−1 is achieved with GlcNAc-conjugated BSA as a model analyte. The developed platform was also successfully applied to analyze O-GlcNAcylation levels in prostate cancer cell line PC-3 and normal cell line RWPE-1. The results obtained by the proposed method are in good agreement with the data from protein microarray assays, demonstrating its great potential for sensitive and reliable O-GlcNAcaylation detection in fundamental research and in cancer diagnosis.
研究领域:
生物化学
·
分析化学
·
癌症生物学
·
蛋白质科学
✓ 已验证
产品关联
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2015
·
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
·
分子生物学
·
基因治疗
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2021
·Vol. 46
·期 3
·1295-1307
·
IF 3.591
Zhi-Gang Yin,Xiong-Wei Liu,Hui-Juan Wang,Min Zhang,Xiong-Li Liu,Ying Zhou
A highly efficient synthesis of structurally diverse ortho-acylphenol–diindolylmethane hybrids 3 using carboxylic acid-activated chromones as versatile synthetic building blocks is reported here for the first time, through 1,4-nucleophilic addition and followed by a decarboxylation and pyrone ring opening reaction process. The newly synthesized compounds were evaluated for their in vitro anticancer activity, and most of the compounds displayed good anticancer activities against four tested tumor cells (A549, PC-3, NCI-H1299, Caco-2). Among these compounds, compound 3t displayed the most potent and broad-spectrum anti-proliferative inhibition against the tested cell lines, especially A549 cells, and was more potent than arundine and cisplatin drugs, and had selectivity in cancer cells compared to MRC-5 and HK-2 normal cells. Preliminary mechanism studies showed that compound 3t exerted an anti-tumor effect in A549 cells by inhibiting the proliferation, colony formation and migration of A549 cells, and inducing cycle arrest at the G0/G1 phase and apoptosis. Furthermore, treatment of A549 cells with compound 3t caused increased ROS content and induced MMP collapse; western blot analysis showed that the expression level of p53 was significantly increased; Bax/Bcl-2 ratio and Cyt c were increased, and caspase-9, -3, and PARP were cleaved. These studies showed that compound 3t could induce apoptosis of A549 cells through the mitochondrial pathway, which was related to the activation of p53 and the generation of ROS. Thus, our results indicate that compound 3t may be used as a promising skeleton for the development of new anti-tumour drugs.
研究领域:
药物化学
·
肿瘤学
·
药学
·
细胞生物学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）