Biochemistry and Cell Biology
·
2024
·
IF 2.4
Xiang Chen,Yuan Yao,Guotong Gong,Tianji He,Chenjun Ma,Jingsong Yu
Prostate cancer (PCa) is a complex disease with diverse molecular alterations. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that exhibits pleiotropic roles in PCa, and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent ligand for AhR. While targeting ferroptosis is an innovative PCa therapeutic strategy, the impact of AhR on this process remains unclear. This study aimed to investigate the influence of AhR on lipid peroxidation and ferroptosis. Results showed that TCDD activated AhR, as evidenced by increased CYP1A1 expression, leading to reduced cell viability. TCDD caused mitochondria shrinkage, decreased the GSH/GSSG ratio, and elevated the MDA levels and lipid peroxidation. Interestingly, AhR knockdown reversed these effects, similar to the action of ferroptosis inhibitors. Mechanistically, TCDD suppressed nuclear receptor subfamily 4 group A member 1 (NR4A1) expression, in part due to AhR activation. This suppression subsequently led to a reduction in the expression of the NR4A1 downstream target stearoyl-CoA desaturase 1 (SCD1). NR4A1 overexpression counteracted the effects of TCDD. In vivo, TCDD activated AhR, downregulated NR4A1 and SCD1 expression, induced mitochondria shrinkage, and increased the MDA and 4-hydroxynonenal (4-HNE) levels. In summary, TCDD promotes ferroptosis in androgen-dependent PCa via inhibiting the NR4A1/SCD1 axis, in part dependent on AhR activation.
研究领域:
肿瘤学
·
分子生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULES
·
2017
·Vol. 22
·期 1
·171
·
IF 2.861
Xiangcong Wang,Maocai Yan,Qibao Wang,Huannan Wang,Zhengyang Wang,Jiayi Zhao,Jing Li,Zhen Zhang
Indole-2-carboxylic acid copper complex (ICA-Cu) was successfully prepared and characterized through elemental analysis, IR, UV-Vis,1H-NMR, TG analysis, and molar conductance, and its molecular formula was [Cu2(C9H6O2N)4(H2O)2]·2H2O. The binding ability of ICA-Cu to calf thymus DNA (CT-DNA) was examined by fluorescence spectrometry and the viscosity method. The results indicated that, upon the addition of increasing amounts of CT-DNA, the excitation and emission intensity of ICA-Cu decreased obviously and the excitation spectra shifted towards a long wavelength. ICA-Cu could displace ethidium bromide (EB) from the EB-DNA system, making the fluorescence intensity of the EB-DNA system decrease sharply; the quenching constantKSVvalue was 3.99 × 104M−1. The emission intensity of the ICA-Cu-DNA system was nearly constant, along with the addition of Na+in a series of concentrations. The fluorescence of the complex could be protected after the complex interacted with DNA. A viscosity measurement further supported the result that the ICA-Cu complex may interact with DNA in an intercalative binding mode. The antioxidant activities of ICA-Cu were evaluated by a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, a hydroxyl radical (OH) scavenging assay, and a 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) assay. The ICA-Cu exhibited the highest inhibitory effects on the ABTS radical (94% inhibition at 60 µM), followed by OH and DPPH radicals (the degrees of inhibition being 71% and 56%, respectively). The in vitro cytotoxicity activity of ICA-Cu against two human breast cancer cell lines, MDA-MB-231 and MCF-7, was investigated by 3-[4,5-dimethyltiazol2-yl]-2.5-diphenyl-tetrazolium bromide (MTT) assay and cellular morphological analysis. The results showed that, upon increasing the concentration of ICA-Cu, an increase was observed in growth-inhibitory activity and the inhibition percentage were greater than 90% at 20 µM in both cell lines. Also, cellular morphological changes in the two cell lines agreed with the cytotoxicity results.Keywords:DNA-binding;antioxidant;anticancer;indole-2-carboxylicacid;copper(II) complexes
研究领域:
化学
·
生物化学
·
药理学
·
癌症研究
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2016
·
IF 8.387
Rong Sun,Song Shen,Yun-Jiao Zhang,Cong-Fei Xu,Zhi-Ting Cao,Long-Ping Wen,Jun Wang
Cancer stem cells (CSCs) have garnered increasin g attention over the past decade, as they are believed to play a crucial role in tumor initiation, progression and metastasis, relapse and drug resistance. Therapeutic strategies which simultaneously exterminate both bulk tumor cells and the rare CSC subpopulation may produce striking response and result in long-term tumor remission. Accumulating evidence provides insight into the function of autophagy in maintenance, plasticity and survival of CSCs. The role of autophagy in the susceptibility of breast CSCs to chemotherapeutics was investigated in the present work, reduced ‘stemness’ and increased susceptibility to chemotherapy drugs (doxorubicin, DOX and docetaxel, DTXL) were observed after chloroquine (CQ)-mediated autophagy inhibition in sorted ALDH hi cells of breast cancer cell line MDA-MB-231. We further proved that nanoparticle-mediated autophagy inhibition promoted the efficacy of chemotherapeutics against ALDH hi MDA-MB-231 cells in vitro . Administration of drug delivery systems significantly prolonged the circulation half-life and augmented enrichment of two different drugs in tumor tissues and ALDH hi cells. More importantly, compared with single treatment, the combined delivery systems NP CQ /NP DOX and NP CQ/DOX (NP CQ /NP DTXL and NP CQ/DTXL ) showed most effective and persistent tumor growth inhibitory effect by eliminating bulk tumor cells as well as CSCs ( p < 0.01) in an MDA-MB-231 orthotopic tumor murine model. Therefore, our research provides new insights into the nanoparticle-facilitated combination of autophagy inhibition and chemotherapy for effective therapy of breast cancer.
研究领域:
肿瘤学
·
药理学
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纳米技术
·
癌症生物学
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOPARTICLE RESEARCH
·
2013
·Vol. 15
·期 10
·1-10
·
IF 2.175
Li Jia,An Yan-Li,Zang Feng-Chao,Zong Shen-Fei,Cui Yi-Ping,Teng Gao-Jun
We report a composite nanoprobe based on silica-coated magnetic nanoparticles (NPs) for distinguishing breast cancers at different HER2 statuses. The nanoprobe has a core–shell structure, with Fe 3 O 4 NPs as the magnetic core and dye-embedded silica as the fluorescent shell, whose average size is about 150 nm. Besides, the outmost surfaces of the probes were modified with specific antibodies to endow the probe with a targeting ability. With such a structure, the nanoprobe can accomplish dual mode targeting of human breast cancer cells based on fluorescence and magnetic resonance imaging (MRI). In the experiments, three human breast cancer cell lines were used to test the targeting ability of the nanoprobe. Specifically, SKBR3 cells with a high HER2 expression level were used as the model target cells, while MCF7 cells with a lower HER2 expression levels and HER2-negative MDA-MB-231 cells were used as the controls. Both the fluorescence and MRI imaging results confirmed that the nanoprobe can distinguish three cancer cell lines with different HER2 expression levels. With the dual mode imaging and specific targeting properties, we anticipate that the presented nanoprobe may have a great potential in the diagnosis and treatment of cancerous diseases.
研究领域:
癌症研究
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纳米技术
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医学成像
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生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2020
·
IF 3.723
Yu Miao,Yanling Wu,Yingjin Jin,Mengze Lei,Jixing Nan,Xue Wu
Liver fibrosis is a common pathological consequence of liver injury, which increases liver failure-related morbidity and mortality. Hence, anti-fibrotic treatment is urgently needed. Oxidative stress plays a pivotal role in the progression of liver fibrosis. Thus, targeting ROS may be an effective strategy for liver fibrosis treatment. In this study, we investigated four benzoquinones derivatives, including 5-isopropyl-2-methyl-1,4-benzoquinone (TQ), 2-tert-butyl-1,4-benzoquinone ( t Bu-Q) 2,5-dimethyl-p-benzoquinone (Dime-Q) and p-benzoquinone (Ph-Q), as well as the evaluation of their antioxidant activity and anti-fibrotic effects on activated hepatic stellate cells and TAA-induced mice. Electrochemical analysis showed that all compounds possessed antioxidant property. The result was first confirmed by in vitro experiments, which revealed potential anti-fibrotic activity of all four compounds at the cellular level. Benzoquinone derivatives act as ROS-scavenging molecules, which modulated the TLR4-CD14 signaling pathway to inhibit the expression of procaspase-1 and IL-1β in cells, induced apoptosis via a mitochondrial pathway by upregulating the ratio of Bax/Bcl-2 and by activating caspase-3, as well as inhibited the expression of the anti-apoptotic proteins FLIP and XIAP in activated LX-2 cells. In addition, a TAA (Thioacetamide)-induced mouse model was used to further validate the results. Treatment with benzoquinone derivatives significantly decreased the levels of liver injury markers and lipid peroxidation caused by excessive ROS, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA). Moreover, treatment with benzoquinone derivatives significantly inhibited extracellular matrix (ECM) deposition and downregulated the mRNA and protein expression of liver fibrosis markers, such as collagen I, alpha-smooth muscle actin (α-SMA), and TIMP-1. In summary, these results indicate that benzoquinone derivatives may act as potential therapeutic drugs against liver fibrosis.
研究领域:
药理学
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肝病学
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF SEPARATION SCIENCE
·
2024
·Vol. 47
·期 21
·e70014
·
IF 2.8
Binhong He,Fengying Ye,Jieqing Feng,Ting Zhou
Lipid extraction of complex biological samples is essential for high-quality data in liquid chromatography-mass spectrometry (LC-MS)-based lipidomics. This study introduces a three-phase liquid extraction (3PLE)-ultra-high-performance LC coupled with quadrupole time-of-flight tandem MS method. This method was successfully applied to lipidomics analysis of breast cancer cells, including highly metastatic MDA-MB-231 and slightly metastatic MCF7 cells. The 3PLE method employed an n -hexane/methyl tert-butyl ether/acetonitrile/water solvent system that formed one aqueous and two organic phases. Neutral and polar lipids were enriched in the upper and middle organic phases, respectively, and combined for detection, thereby reducing analysis time. Compared with the Bligh and Dyer method, 3PLE achieved higher sensitivity and detected more features, with over a 50% increase in the relative abundance of nearly 50% of the differential lipids. In total, 21 differential lipids were identified in the MDA-MB-231 group and 22 in the MCF7 group compared to normal breast epithelial cells (MCF10A). Pathway analysis suggested that lipid changes in breast cancer cells were associated with glycerophospholipid metabolism, arachidonic acid metabolism, sphingolipid metabolism, and linoleic acid metabolism. The study presents a highly efficient lipidomics method, providing a scientific foundation for understanding breast cancer pathogenesis and aiding in diagnosis.
研究领域:
癌症生物学
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分析化学
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质谱分析
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脂质代谢
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2024
·
IF 6.7
Yunfan Zhou,Xue Wei,Jun Chen,Hanzhi Xiong,Dandan Sui,Xu Chen,Wensheng Yang
Breast cancer is a malignant tumor, with various subtypes showing different behaviors. Endogenous H2O2 is an important marker of tumor progression, which makes it important to study the relationship between breast cancer subtypes and H2O2 for pathogenesis and treatment strategies, but this has rarely been reported so far. In this work, we constructed a three-dimensional (3D) electrochemiluminescence (ECL) sensing platform for the detection of H2O2 released from two typical subtypes of breast cancer cells (MCF-7 cells for luminal A-type and MDA-MB-231 cells for three negative breast cancers, TNBCs). To adequately replicate the tumor microenvironment, the peptide hydrogel was introduced as a scaffold for 3D cell culture. The titanium foam (TF) was used as a 3D electrode to better match the 3D culture substrate. N-(4-Aminobutyl)-N-ethylisoluminol (ABEI) was selected as the ECL emitter and assembled into the peptide hydrogel by hydrogen bonding and π-stacking, which resulted in a stable and homogeneous distribution of ABEI along the hydrogel fibers. Furthermore, basic amino acids were introduced to provide alkaline microenvironment for ABEI. Therefore, ABEI exhibited high ECL efficiency, resulting in a high sensitivity with an ultralow detection limit of 0.023 nM (S/N = 3) for H2O2 of the proposed ECL biosensor. MCF-7 and MDA-MB-231 cells were cultured in a 3D peptide hydrogel/ABEI/TF electrode, respectively, and endogenous H2O2 was successfully monitored. A notably significant difference of H2O2 released between MDA-MB-231 cells and MCF-7 cells without stimulation but similar extra release with stimulation were observed. These findings may help understand the physiological mechanisms behind the various subtypes and reactive oxygen species (ROS)-related treatment for breast cancer.
研究领域:
生物医学工程
·
癌症生物学
·
分析化学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Advanced Research
·
2024
·
IF 11.4
Guiqin Huang,Yawen Cai,Menghui Ren,Xiaoyu Zhang,Yu Fu,Run Cheng,Yingdi Wang,Mingxing Miao,Lingpeng Zhu,Tianhua Yan
Introduction Triple-negative breast cancer (TNBC) is the primary cause of breast cancer-induced death in women. Literature has confirmed the benefits of Salidroside (Sal) in treating TNBC. However, the study about potential therapeutic targets and mechanisms of Sal-anchored TNBC remains limited. Objective This study was designed to explore the main targets and potential mechanisms of Sal against TNBC. Methods Network pharmacology, bioinformatics, and machine learning algorithm strategies were integrated to examine the role, potential targets, and mechanisms of the Sal act in TNBC. MDA-MB-231 cells and tumor-bearing nude mice were chosen for in vitro and in vivo experimentation. Cell viability and cytotoxicity were determined using CCK-8, LDH test, and Calcein-AM/PI staining. Antioxidant defense, lipid peroxidation, and iron metabolism were explored using glutathione, glutathione peroxidase, malondialdehyde (MDA), C11-BODIPY 581/591 probe, and FerroOrange dye. Glutathione peroxidase 4 (GPX4) or stearoyl-CoA desaturase 1 (SCD1) overexpression or nuclear receptor co-activator 4 (NCOA4) deficiency was performed to demonstrate the mechanism of Sal on TNBC. Results The prediction results confirmed that 22 ferroptosis-related genes were identified in Sal and TNBC, revealing that the potential mechanism of the Sal act on TNBC was linked with ferroptosis. Besides, these genes were mainly involved in the mTOR, PI3K/AKT, and autophagy signaling pathway by functional enrichment analysis. The in vitro validation results confirmed that Sal inhibited TNBC cell proliferation by modulating ferroptosis via elevation of intracellular Fe 2+ and lipid peroxidation. Mechanistically, Sal sensitized TNBC cells to ferroptosis by inhibiting the PI3K/AKT/mTOR axis, thereby suppressing SCD1-mediated lipogenesis of monounsaturated fatty acids to induce lipid peroxidation, additionally facilitating NCOA4-mediated ferritinophagy to increase intracellular Fe 2+ content. The GPX4 or SCD1 overexpression or NCOA4 deficiency results further supported our mechanistic studies. In vivo experimentation confirmed that Sal is vital for slowing down tumor growth by inducing ferroptosis. Conclusions Overall, this study elucidates TNBC pathogenesis closely linked to ferroptosis and identifies potential biomarkers in TNBC. Meanwhile, the study elucidates that Sal sensitizes TNBC to ferroptosis by SCD1-mediated lipogenesis and NCOA4-mediated ferritinophagy, regulated by PI3K/AKT/mTOR signaling pathways. Our findings provide a theoretical basis for applying Sal to treat TNBC.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
·
2021
·
IF 4.86
Jie Tang,Mingrong Bei,Jia Zhu,Guangtao Xu,Deqing Chen,Xin Jin,Jianzhong Huang,Jingjian Dong,Lili Shi,Long Xu,Bo Hu
Cadmium (Cd) exposure can exert an impact on carcinogenicity of breast cancer, however, the mechanism is not fully understood in triple-negative breast cancer (TNBC). We performed a TNBC MDA-MB-231 cell model and assessed the toxic effect of Cd exposure (0, 10, 20, 50, 60, 80 μM). Cd reduced cell viability in a time- and dose-dependent manner, followed by cell cycle arrest in S phase with alterations of cyclin 1A1, cyclin 1D1 and CDK2. Lactate dehydrogenase (LDH) release, apoptosis and pyroptosis were increased, which were relieved by z-VAD. Elevated ROS and NLRP3, caspase-1, IL-1β and IL-18 were detected, which was attenuated by N-acetylcysteine. Increased bax and decreased caspase-8, caspase-9 and caspase-3 were found. gasdermin E (GSDME) was activated with cleavage of GSDME-NT, which was retarded by z-VAD. Additionally, p38 MAPK signaling pathway was activated. Our data demonstrate GSDME-activated pyroptosis in Cd toxicity, implying a potential impact on TNBC.
研究领域:
毒理学
·
肿瘤学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2018
·
IF 3.909
Wan Li,Zheng-Nan Cai,Shomaila Mehmood,Ya Wang,Wen-Juan Pan,Wen-Na Zhang,Yong-Ming Lu,Yan Chen
Oxidative stress is considered to involve cell death in severe pulmonary diseases like idiopathic pulmonary fibrosis (IPF). Polysaccharide FMP-1 from Morchella esculenta can exert significant antioxidant activity. However, its effects on alveolar epithelial cells remain unperceived. Herein, the effects of FMP-1 against H 2 O 2 -induced oxidative damage in human alveolar epithelial A549 cells were investigated. FMP-1 could inhibit H 2 O 2 -induced cytochrome C and Caspase-3 release to prevent cell apoptosis via attenuation of MDA and ROS levels, and enhancement the enzymatic activities of SOD and T-AOC. Furthermore, the underlying molecular mechanisms were clarified. The phosphorylation of AKT and the nuclear translocation of Nrf2 were observed to be promoted by FMP-1 as well as the level of HO-1. These findings suggested that FMP-1 attenuate cellular oxidative stress through PI3K/AKT pathway, and FMP-1 could be explored as natural potential antioxidants to lower oxidative stress relevant to the progression of IPF.
研究领域:
药理学
·
细胞生物学
·
呼吸病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Veterinary Science
·
2022
·
IF 3.471
Wang Zixi,Tang Yanfang,Long Lina,Zhang Huihua
In order to reduce the negative effects caused by oxidative stress on broilers, it is particularly important to find ways to alleviate oxidative stress. As a natural plant extract, L-theanine has a variety of biological effects, such as improving antioxidant capacity, promoting growth, and enhancing immunity and antitumor. This trial evaluated the effects of dietary supplementation of L-theanine on growth performance, antioxidation, meat quality, and intestinal microflora in 817 White Feather Broilers. A total of 108 21-day-old 817 broilers with similar body weight (BW) were randomly divided into three groups with six replicates per group and six chickens within each replicate. The three groups were corn-soybean-based diet (NC group); basal diet plus drinking water with 30 mg hydrocortisone/kg (PC group); and basal diet supplemented with 400 mg L-theanine/kg plus drinking water with 30 mg hydrocortisone/kg (LT group). Compared with the NC group, from 21 to 24 days of age, the PC and LT groups had decreased BW, average daily gain (ADG), and average daily feed intake (ADFI), and increased feed to gain ratio (F/G; p < 0.05). At 24 days of age, the LT group had improved superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in serum as compared to the NC group (p < 0.05). The LT group broilers also had significantly higher concentrations of malondialdehyde (MDA) in serum and liver (p < 0.05). On the 42nd days, the PC group had lower PH45min (p < 0.05) than the NC and LT groups and higher cooking loss and shear force (p < 0.05). Moreover, the villi height of the PC group was significantly lower in jejunum than the NC group (p < 0.05). The LT group had a higher ZO-1 content in duodenum than the NC and PC groups (p < 0.05). The activity of GSH-Px in the liver of the LT group was increased than in the PC group (p < 0.05). The relative abundance of Firmicutes in the LT group was significantly higher than in the NC and PC groups (p < 0.05). These results suggested that the effects of acute oxidative stress on growth performance and meat quality of broilers are continuous, and dietary supplementation of L-theanine could improve the growth performance and meat quality, enhance the intestinal mucosal barrier and antioxidant capacity, and improve the composition of the intestinal flora of broilers caused by acute oxidative stress.
研究领域:
家禽科学
·
营养学
·
动物生理学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
·
2022
·
IF 8.943
Yan Li,Yutan Chu,Hongyu Sun,Qiongli Bao,Yizong Huang
Arsenic (As) is a common environmental pollutant that seriously interferes with the normal growth of organisms. There is an urgent need to take environment-safe and efficient strategies to mitigate As toxicity. Melatonin (MT) is a pleiotropic molecule that regulates plant growth and organ development and alleviates heavy metal stresses. The experiment aims to explore the mechanism of MT in reducing arsenite toxicity by hydroponic rice seedlings. The results showed that MT application reduced the As content in rice roots and shoots by 26.4% and 37.5%, respectively, and mainly decreased As content in the soluble fractions of the rice root cell. MT application also increased the As content of chelated-soluble pectin and alkali-soluble pectin in the cell wall by 14.7% and 74.4%, respectively. It promoted the generation of the functional group of the root cell walls by the FTIR analysis, indicating that MT may promote the fixation of As on the cell wall. Meanwhile, MT contributed to scavenging excess H 2 O 2 , reducing MDA content, and maintaining normal morphology of root cells by stimulating SOD, POD and CAT activities and increasing the level of GSH. The research deepens our understanding of how MT participates in maintaining redox homeostasis in rice cells, reducing As toxicity, and decreasing As concentration in rice seedlings, thereby providing more possibilities for reducing As accumulation in rice.
研究领域:
植物生理学
·
环境毒理学
·
农学
✓ 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）