ENVIRONMENTAL RESEARCH
·
2021
·
IF 6.498
Mengyuan Qi,Xiaodan Ma,Bin Liang,Liying Zhang,Deyong Kong,Zhiling Li,Aijie Wang
Sulfonamide antibiotics (SAs) have been produced and consumed on a large scale over the last few decades. SAs are a typical class of refractory contaminants that are omnipresent in various environments. Although several [phenyl]-SA-degrading bacteria and their corresponding genomes have been documented, limited genetic information is available for the degraders of heterocyclic products (e.g., 3-amino-5-methylisoxazole [3A5MI] produced via sulfamethoxazole [SMX] catabolism). In this study, the previously isolated SMX-mineralizing bacterial partners, Paenarthrobacter sp. P27 (responsible for the initial cleavage of the -C-S-N- bond of SMX and further degradation of [phenyl]-SMX) and Norcardiodes sp. N27 (responsible for 3A5MI catabolism), were further studied and their complete genomes were sequenced. Complete degradation and bacterial growth were verified by pure-culture experiments with SMX or 3A5MI as the sole carbon, nitrogen, and energy source. By cross-feeding strains P27 and N27, complete catabolism of SMX could be achieved over a wide range of initial SMX concentrations. Moreover, strain P27 was capable of transforming the additional nine SA representatives into their corresponding nitrogen-containing heterocyclic products, strongly indicating the broad substrate spectrum and marked bioremediation potential of strain P27. The genome of strain P27 contained the highly homologous monooxygenase gene cluster, sadABC , which initially attacked the sulfonamide molecules. The complete genome sequences of the two important degraders will benefit future research centering on the molecular mechanism underlying advanced SMX mineralization and will aid in further understanding the interspecific interactions and metabolite exchanges for the optimization of artificially constructed synthetic functional microbiomes.
研究领域:
环境微生物学
·
基因组学
·
污染治理
✓ 已验证
DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2025
·
IF 5.4
Xiangyun Tan,Yuan Yang,Junjie Hu,Yan Meng,Liang Chen,Guohua Zheng,Han Xiao,Zhenpeng Qiu
Intrahepatic cholangiocarcinoma (iCCA) is a malignant liver tumor with insidious onset, limited treatments, and poor prognosis. Recent studies show celecoxib exerts marked cytotoxic effects on cholangiocarcinoma cell lines, suggesting its potential as an iCCA therapy. However, the potential molecular and cellular mechanisms that link celecoxib treatment to its toxicological outcomes remain unclear. In this study, we induced iCCA in mice by overexpressing AKT and YapS127A (hereafter referred to as AKT/YapS127A) and administered celecoxib continuously to evaluate its antitumor effects in vivo . The results demonstrate that celecoxib effectively inhibited tumor growth in AKT/YapS127A-driven iCCA mice. Mechanistically, celecoxib boosted levels of cell cycle inhibitors p21 Waf1/Cip1 and p27 Kip1 , leading to cell cycle arrest. It also promoted apoptosis by downregulating the expression of anti-apoptotic proteins Mcl-1 and Bcl-2. These effects were associated with the modulation of the AKT/mTORC1 signaling pathway. Consistently, celecoxib recapitulated AKT/mTORC1 inhibition and subsequent cell cycle/apoptotic regulator alterations in iCCA cell lines. Collectively, our study elucidates the molecular mechanisms through which celecoxib exerts its anti-tumor effects in iCCA, demonstrating its capacity to induce cytotoxic outcomes via the precise regulation of the AKT/mTORC1 pathway. These findings deepen understanding of the toxicological actions of celecoxib and provide critical insights for developing targeted iCCA therapies.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
肝病学
·
细胞信号传导
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Oncology
·
2022
·
IF 4.501
Li Zheng,Yu Wu,Fu Wang,Hui Shi,Bo Xu,Aihua Yang
Objective. To study the pharmacological activity and the mechanism of action of natural compounds derived from 6,7-dimethoxycoumarin on the differentiation of human chronic myeloid leukemia K562 cells. Methods. We use MTT assay (Sigma-Aldrich, USA) to detect cell viability; use flow cytometry to analyze DNA content for cell cycle analysis; use benzidine staining to synthesize hemoglobin to determine K562 cell differentiation; use western blot analysis and qPCR to detect the expression levels of FOX03, P27, CDK4, and their phosphorylation; and use the AOBS laser scanning confocal system (Leica, Wetzlar, Germany) to analyze and quantify the number of positive green spots. The statistical methods used are one-way analysis of variance (ANOVA) and Dunnett’s test to analyze within and between groups. Results. In order to explore the effect of 6,7-dimethoxycoumarin on the differentiation of K562 cell erythrocytes, it was concluded that 6,7-dimethoxycoumarin promotes the differentiation of K562 cell erythrocytes; the proliferation of K562 cells was detected by MTT method, and the results showed that 6,7-dimethoxycoumarin can inhibit the proliferation of K562 cells; to evaluate the effect of 6,7-dimethoxycoumarin on the proliferation of K562 cells, the results showed that 6,7-dimethoxycoumarin increased the expression of FOXO3, P27, CDK4, and CDK65, and decreased the phosphorylation of CDK4 and CDK6 proteins. To further explore the effect of knocking out FOXO3 on cell differentiation, the results show that 6,7-dimethoxycoumarin can reduce the differentiation and proliferation of K562 cells by increasing the expression of FOXO3. Conclusion. This study extended the understanding of the pharmacological activity of 6,7-dimethoxycoumarin and may provide a potential new target for the treatment of chronic myelogenous leukemia. However, we still need to further study the specific molecular capabilities of 6.7 dimethylcoumarin to understand their possible capture mechanism.
研究领域:
肿瘤学
·
血液学
·
分子生物学
·
药理学
✓ 已验证
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
JOURNAL OF BIOLOGICAL CHEMISTRY
·
2025
·
IF 3.9
Mengna Zhu,Lin Huang,Si Sun,Mengqing Chen,Jing Cai,Yuan Zhang,Lufang Wang,Liqiong Cai,Minggang Peng
Platinum-based chemotherapy remains the cornerstone of the treatment of epithelial ovarian cancer (EOC); however, platinum resistance is a major cause of tumor recurrence and mortality in EOC patients. This study reports the mechanism by which EOC cells develop resistance to cisplatin by inhibiting the ferroptosis. Immunohistochemical analysis of human EOC tissues revealed that low p27 expression significantly correlated with poor response to chemotherapy and unfavorable patient prognosis. Functionally, CRISPR/Cas9-mediated p27 knockout increased cisplatin resistance in EOC cells in both in vitro and in vivo models. RNA sequencing and functional assays demonstrated that p27 enhanced cisplatin sensitivity by facilitating drug-induced ferroptosis in EOC cells. Mechanistically, luciferase reporter assays demonstrated that p27 enhanced the transcriptional activity of cytochrome b-245 heavy chain (CYBB), a key positive regulator of ferroptosis. Moreover, we found that the small molecule inhibitor SKPin C1 significantly enhanced cisplatin’s antitumor effect by preventing p27 degradation, both in vitro and in vivo . In conclusion, our findings emphasize the critical role of p27 in triggering ferroptosis, thereby sensitizing EOC cells to cisplatin therapy. These results suggest that therapeutic strategies aimed at enhancing p27 levels may represent a promising approach to overcoming chemoresistance in EOC.
研究领域:
肿瘤学
·
分子生物学
·
癌症治疗学
·
细胞死亡机制
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Oncology Letters
·
2018
·Vol. 17
·期 2
·2498-2506
·
IF 1.664
Xuefeng Yang,Handong Huang,Maijian Wang,Xingbin Zheng,Ming Xie,Jie Xu
Previous studies have indicated the potential role of estrogen in the development and prognosis of colorectal cancer (CRC). Nonylpheno (NP) is an endocrine‑disrupting chemical, which may influence the development of estrogen‑dependent types of cancer. However, the molecular mechanism of NP in the development of CRCs remains unclear. In the present study, various concentrations of NP were used to treat COLO205 CRC cells, and the expression of protein kinase C ζ (PKCζ) was knocked down using PKCζ small interfering RNA. The effects of NP in various concentrations on the cell cycle and apoptosis of COLO205 cells were examined, and the change in the expression level of PKCζ was analyzed. The results indicated that NP may significantly induce proliferation of COLO205 CRC cells, and significantly reduce cell apoptosis. However, suppression of PKCζ expression may inhibit proliferation, while NP could reduce this inhibition. The results of a western blot analysis indicated that the expression level of cyclin D1 and E were significantly increased following NP treatment, and the expression of p27 was significantly decreased. The phosphorylation of PKCζ and extracellular‑signal‑regulated kinase (ERK)1/2 was significantly increased following NP treatment in a dose‑dependent manner. Overall, NP induced human CRC COLO205 cell proliferation and inhibited the apoptotic rate of COLO205 cells by increasing the activity of PKCζ and ERK1/2.
研究领域:
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
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2022
·
IF 5.062
Yan Wang,Chen Zhang,Meng Xiao,Kumar Ganesan,Fei Gao,Qingqing Liu,Zhen Ye,Yue Sui,Feng Zhang,Kunhua Wei,Yaobin Wu,Jianmin Wu,Bing Du,Cong Xu,Yan Li,Peng Li,Jinming Zhang,Jianping Chen
Treatment of aggressive triple-negative breast cancer (TNBC) is still challenging. Isoliquiritigenin (ISL) is a water-insoluble bioactive compound possessing high anti-TNBC capacity with less toxicity. The present study aimed to develop a safe and effective oral drug delivery system to improve the oral efficacy of ISL for TNBC therapeutics. ISL-loaded zein phosphatidylcholine hybrid nanoparticles ( [email protected] NPs) were constructed by a one-step solvent evaporation method. Optimization and characterization of [email protected] NPs were performed. Cellular uptake in vitro and biodistribution of ZLH NPs in vivo were investigated. The pharmacokinetics of [email protected] NPs in terms of ISL content in the plasma, organs, and tumor tissues were validated, and the anti-TNBC efficacy was evaluated. Encapsulation efficiency (96.75 ± 1.41%) and drug loading efficiency (6.56 ± 0.83%) were found in [email protected] NPs. [email protected] NPs were able to enhance the absorption of ISL in the tumor sites. Moreover, the upregulation of p27 and downregulation of EGFR and CDK4 were observed in [email protected] NPs treated tumors. Collectively, oral intake of [email protected] NPs would be translated into a potential clinical therapy strategy against TNBC.
研究领域:
肿瘤学
·
药剂学
·
纳米技术
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Metallomics
·
2019
·Vol. 12
·期 2
·173-182
·
IF 3.571
Lv Xiaoguang,Zheng Qiaoqiao,Li Ming,Huang Zhiwei,Peng Min,Sun Jing,Shi Ping
Clioquinol is recently considered to be the most promising drug for treating cancer and neurodegenerative diseases. However, its mode of action varies from different disease models. In this study, we found that clioquinol inhibited cell growth in human neurotypic SHSY-5Y cells, which was attributed to both S-phase cell-cycle arrest and autophagic cell death. Clioquinol increased the intracellular contents of iron and zinc as well as calcium as measured by ICP-AES. Staining of Fluo-3 confirmed an increase in the level of calcium. Analysis of the metal-binding ability of clioquinol showed that it was not a chelating agent of calcium ions and the elevation of intracellular calcium content is not achieved by clioquinol as an ionophore. CaCl2 could simulate or even aggravate the cytotoxicity of clioquinol and it increased S-phase cell cycle arrest induced by clioquinol in a concentration dependent manner. Staining of acridine orange demonstrated that autophagy induced by clioquinol was not affected by addition of calcium ions. In contrast, the intracellular calcium ion chelator BAPTA-am abolished the clioquinol-induced S phase arrest and reduced the cell death caused by clioquinol. The WB assay of cell cycle-related proteins (CDK2, p21 and p27) further confirmed that S phase arrest is positively correlated with intracellular calcium elevation, which was due to the alterations of the mRNA and protein levels of calcium pumps (SERCA and SPCA). Taken together, these data indicate that clioquinol regulates the level of intracellular calcium ions to induce S-phase cell cycle arrest in human SH-SY5Y cells. Our results demonstrate for the first time that an increase of intracellular calcium content is one of the mechanisms of clioquinol in the inhibition of human neurotypic SHSY-5Y cells.
研究领域:
肿瘤学
·
神经科学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CANCER SCIENCE
·
2021
·Vol. 112
·期 8
·3218-3232
·
IF 6.716
Dan-Hua He,Yu-Fei Chen,Yi-Le Zhou,Shi-Bing Zhang,Ming Hong,Xianjun Yu,Su-Fen Wei,Xiang-Zhen Fan,Si-Yi Li,Qi Wang,Yongzhi Lu,Yong-Qiang Liu
Skp2 is overexpressed in multiple cancers and plays a critical role in tumor development through ubiquitin/proteasome-dependent degradation of its substrate proteins. Drugs targeting Skp2 have exhibited promising anticancer activity. Here, we identified a plant-derived Skp2 inhibitor, betulinic acid (BA), via high-throughput structure-based virtual screening of a phytochemical library. BA significantly inhibited the proliferation and migration of non–small cell lung cancer (NSCLC) through targeting Skp2-SCF E3 ligase both in vitro and in vivo. Mechanistically, BA binding to Skp2, especially forming H-bonds with residue Lys145, decreases its stability by disrupting Skp1-Skp2 interactions, thereby inhibiting the Skp2-SCF E3 ligase and promoting the accumulation of its substrates; that is, E-cadherin and p27. In both subcutaneous and orthotopic xenografts, BA significantly inhibited the proliferation and metastasis of NSCLC through targeting Skp2-SCF E3 ligase and upregulating p27 and E-cadherin protein levels. Taken together, BA can be considered a valuable therapeutic candidate to inhibit metastasis of NSCLC.
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
Metallomics
·
2018
·Vol. 10
·期 6
·838-845
·
IF 4.069
Sun Pengcheng,Wang Song,Wang Jian,Sun Jing,Peng Min,Shi Ping
Chemerin exhibits a tumor-inhibitory role in hepatocellular carcinoma. However, the effect of chemerin on essential metal elements in hepatic cells remains unclear. In our study, the contents of six important metal ions, including potassium, calcium, sodium, magnesium, iron and zinc, were detected in human hepatoma SMMC7721 and immortal hepatic QSG7701 cells by ICP-AES. The data showed that chemerin only decreases the content of intracellular iron in SMMC7721 cells. The reduction was due to the blockage of iron entry through the decrease in the mRNA levels of divalent metal transporter 1, iron regulatory proteins and transferrin receptors. Furthermore, the reduction of the cellular iron content induced alterations of p53–p27–p21 signaling to arrest the cell cycle at S phase in SMMC7721 cells treated by chemerin. Conversely, iron addition led to recovery from the inhibitory effect of chemerin on SMMC7721 cells. The results suggest that chemerin plays an important role in inhibiting the cell proliferation of hepatocellular carcinomas by interfering with cellular iron homeostasis in this type of tumors.
研究领域:
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
CHEMOSPHERE
·
2023
·
IF 8.8
Zhen-Ning Zhang,Dan-Lei Yang,Hai Liu,Jue Bi,Ya-Bo Bao,Jiao-Yang Ma,Qin-Xiang Zheng,Dao-Lei Cui,Wei Chen,Ping Xiang
Tris(2-chloroisopropyl) phosphate (TCPP) and Tris(2-chloroethyl) phosphate (TCEP) are the widely used organophosphorus flame retardants indoors and easily accessible to the eyes as the common adhesive components of dust and particle matter, however, hardly any evidence has demonstrated their corneal toxicity. In this study, the adverse effects of TCPP, TCEP, and TCPP + TCEP exposure on human corneal epithelial cells (HCECs) were investigated. The cell viability and morphology, intracellular reactive oxygen species (ROS), cell cycle, and the expressions of cell cycle and pyroptosis-related genes were assessed to explain the underlying mechanisms. Compared to individual exposure, co-exposure to TCPP 20 +TCEP 20 showed higher cytotoxicity with a sharp decrease of >30% in viability and more serious oxidative damage by increasing ROS production to 110.92% compared to the control group. Furthermore, the cell cycle arrested at the S phase (36.20%) was observed after combined treatment, evidenced by the upregulation of cyclin D1 , CDK2 , CDK4 , CDK6 , p21, and p27 . Interestingly, pyroptosis-related genes GSDMD , Caspase-1 , NLRP3 , IL-1β , IL-18 , NLRP1, and NLRC4 expressions were promoted with cell swelling and glowing morphology. Oxidative stress and cell cycle arrest probably acted as a key role in TCPP 20 +TCEP 20 -induced cytotoxicity and pyroptosis in HCECs. Our results suggested that TCPP 20 +TCEP 20 co-exposure induced severer corneal damage, further illustrating its significance in estimating indoor health hazards to humans.
研究领域:
毒理学
·
细胞生物学
·
眼科学
·
环境健康
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Aging-US
·
2019
·
IF 5.515
Yanhua Du,Jun Lin,Rulin Zhang,Wanli Yang,Heng Quan,Lijuan Zang,Yaqin Han,Bing Li,Hong Sun,Jun Wu
Globally, epithelial ovarian cancer (EOC) is the most common gynecological malignancy with poor prognosis. The expression and oncogenic roles of ubiquitin specific peptidase 5 (USP5) have been reported in several cancers except EOC. In the current study, USP5 amplification was highly prevalent in patients with EOC and associated with higher mRNA expression of USP5. USP5 amplification and overexpression was positively correlated with poor prognosis of patients of ovarian serous carcinomas. Disruption of USP5 profoundly repressed cell proliferation by inducing cell cycle G0/G1 phase arrest in ovarian cancer cells. Additionally, USP5 knockdown inhibited xenograft growth in nude mice. Knockdown of USP5 decreased histone deacetylase 2 (HDAC2) expression and increased p27 (an important cell cycle inhibitor) expression in vitro and in vivo . The promoting effects of USP5 overexpression on cell proliferation and cell cycle transition, as well as the inhibitory effects of USP5 overexpression on p27 expression were mediated by HDAC2. Moreover, USP5 interacted with HDAC2, and disruption of USP5 enhanced the ubiquitination of HDAC2. HDAC2 protein was positively correlated USP5 protein, and negatively correlated with p27 protein in ovarian serous carcinomas tissues. Collectively, our data suggest the oncogenic function of USP5 and the potential regulatory mechanisms in ovarian carcinogenesis.
研究领域:
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
危险品化学品经营许可证（带存储）