INTERNATIONAL JOURNAL OF ONCOLOGY
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2023
·Vol. 62
·期 5
·1-21
·
IF 5.2
Ting Xue,Yaodong Chen,Jia Xu,Weiqin Du,Pengzhou Kong,Xinri Zhang
Lung cancer is the leading cause of cancer‑related mortality worldwide. Non‑small cell lung cancer (NSCLC) is the most common pathological subtype of lung cancer and is associated with low 5‑year overall survival rates. Therefore, novel and effective chemotherapeutic drugs are urgently required for improving the survival outcomes of patients with lung cancer. Cyclovirobuxine D (CVB‑D) is a natural steroidal alkaloid, used for the treatment of cardiovascular diseases in Traditional Chinese Medicine. Several studies have also demonstrated the antitumor effects of CVB‑D. Therefore, in the present study, the therapeutic effects of CVB‑D in lung cancer and the underlying mechanisms were investigated using the in vivo xenograft model of NSCLC in nude mice and in vitro experiments with the NSCLC cell lines. Bioinformatics analyses of RNA‑sequencing data, and cell‑based functional assays demonstrated that CVB‑D treatment significantly inhibited in vitro and in vivo NSCLC cell proliferation, survival, invasion, migration, angiogenesis, epithelial‑to‑mesenchymal transition and G2/M phase cell cycle. CVB‑D exerted its antitumor effects by inhibiting the KIF11‑CDK1‑CDC25C‑cyclinB1 G2/M phase transition regulatory oncogenic network and the NF‑κB/JNK signaling pathway. CVB‑D treatment significantly reduced the sizes and weights and malignancy of xenograft NSCLC tumors in the nude mice. In conclusion, the present study demonstrated that CVB‑D inhibited the growth and progression of NSCLC cells by inhibiting the KIF11‑CDK1‑CDC25C‑CyclinB1 G2/M phase transition regulatory network and the NF‑κB/JNK signaling pathway. Therefore, CVB‑D is a promising drug for the treatment of NSCLC patients.
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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细胞生物学
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DOI
PubMed
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 13
·5047
·
IF 4.6
Yan Wang,Youbin Li,Dong Liu,Danyang Zheng,Xiaogang Li,Chang Li,Caihui Huang,Yun Wang,Xuesong Wang,Qifu Li,Junyu Xu
Glioblastoma (GBM) is a deadly brain tumor characterized by signaling dysregulation and aberrant cell cycle control. The CDK4/6-Rb axis is dysregulated in approximately 80% of all GBM cases. In this study, the anti-GBM effect of a novel pyrimidin-2-amine, LH20 was evaluated in vitro using the primary GBM cell lines U87MG and U251. GBM cells were administered LH20 at concentrations of 0.1, 1, 4, 8, 10, 20, 100, and 200 µM for 24 and 48 h, and the proliferation rate was evaluated using a CCK8 assay. Migration, apoptosis, and cell cycle were also assessed using a wound healing assay, Annexin V-FITC/PI apoptosis assay, and cell cycle staining, respectively. The targets of LH20 were predicted using SwissTargetPrediction and molecular docking. Western blotting analysis was performed to confirm the anti-GBM mechanism of LH20. We found that at concentrations of 4, 8, and 10 µM, LH20 significantly inhibited the proliferation and migration of U87MG and U251 cells, induced late phase apoptosis, promoted tumor cell necrosis, and arrested the G2/M phase of the cell cycle. LH20 also inhibited CDK4 and CDK6 activities by decreasing the phosphorylation of Rb. Our results suggest LH20 as a potential treatment strategy against GBM.Keywords:LH20;glioblastoma;apoptosis;G2/M;mitochondrial;CDKs
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
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DOI
PubMed
高影响因子
JOURNAL OF BASIC MICROBIOLOGY
·
2022
·Vol. 62
·期 11
·1360-1370
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IF 2.65
Jiahe Fan,Chaoyi Lv,Zhizhou Li,Mengru Guo,Yichen Yin,Hui Wang,Wei Wang,Shiwei Sun
α-Glucosidase is the key enzyme on carbohydrate metabolism, and its bioactive inhibitors are supposed to be an effective therapeutic for type 2 diabetes mellitus. During our continuing study for discovering α-glucosidase inhibitors, a fungus GDZZ-G2 which is derived from a medicinal plant Callicarpa kwangtungensis Chun, exhibited significant inhibition on α-glucosidase. The strain was identified as Fusarium incarnatum by morphological and molecular methods. Further bioassay-guided fractionation result in six known secondary metabolites ( 1 - 6 ). All the compounds except 4 were isolated from F . incarnatum for the first time. Among them, an anthraquinonoid ( S )-1,3,6-trihydroxy-7-(1-hydroxyethyl)anthracene-9,10-dione (compound 1 ) exhibited strong inhibitory effect against α-glucosidase (IC 50 = 77.67 ± 0.67 μΜ), compared with acarbose (IC 50 = 711.8 ± 5 μΜ). An enzyme kinetics analysis revealed that compound 1 was an uncompetitive inhibitor. Besides, docking simulations predicted that compound 1 inhibited α-glucosidase substrate complex by binding Gln322, Gly306, Thr307, and Ser329 through hydrogen-bond interactions. Our findings suggested that compound 1 can be considered a lead compound for further modifications and the development of a new effective drug candidate in the treatment of type 2 diabetes mellitus.
研究领域:
药理学
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微生物学
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天然产物化学
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DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2017
·Vol. 16
·期 2
·2069-2074
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IF 1.692
Huijun Liu,Weiwei Liu,Xin Zhou,Chongde Long,Xielan Kuang,Jie Hu,Yan Tang,Lanying Liu,Jia He,Zixin Huang,Yuting Fan,Guorong Jin,Qingjiong Zhang,Huangxuan Shen
Oxidative damage is a key factor for the pathogenesis of age‑related macular degeneration (AMD), therefore, anti-oxidative stress is a valuable method for the prevention or treatment of AMD. The aim of the present study was to reveal the protective mechanism of lutein on retinal pigment epithelium (RPE) cells subjected to oxidative stress. Acute retinal pigment epithelial 19 (ARPE‑19) cells were exposed to oxidative stress induced by H2O2 following lutein pretreatment. The activities of caspases, level of intracellular reactive oxygen species (ROS) and cell cycle were analyzed using flow cytometry. The expression levels of cell cycle regulatory proteins and inflammation‑associated genes were detected using western blot and reverse transcription‑polymerase chain reaction analyses, respectively. The data showed that oxidative stress reduced cell viability, and increased total apoptosis and ROS generation, however, lutein prevented cells from oxidative stress‑induced damage. In addition, oxidative damage triggered G2/M phase arrest of the ARPE‑19 cells, which was reversed by lutein in a concentration‑dependent manner, through the activation of cyclin‑dependent kinase 1 and cell division cycle 25C, and degradation of cyclin B1. These results demonstrated that lutein may be an effective antioxidant, which can be applied in the prevention of AMD, or other age-related diseases associated with oxidative damage.
研究领域:
眼科学
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细胞生物学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
Frontiers in Veterinary Science
·
2025
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IF 2.9
Mengjuan Chen,Hui Han,Mengke Qin,Huixin Li,Qiqi Lu,Xin Huang,Qingda Meng,Shanshan Xie
Introduction: Current management of canine mammary tumors (CMTs) remains reliant on surgical resection and chemotherapy. However, these strategies are often limited by high recurrence rates and systemic toxicity. Addressing these limitations requires urgent development of safer and more effective therapeutics. Pseudolaric acid B (PAB), a bioactive compound extracted from the roots of the Pseudolarix kaempferi Gord., has garnered attention for its broad-spectrum antitumor activity and favorable pharmacokinetic profile, and it has shown promise in inhibiting the growth of a variety of tumors, including breast cancer. The aim of this study was to investigate the anticancer effects of PAB on canine mammary tumor U27 cells and its underlying mechanisms.Methods and results: In vitro analyses demonstrated that PAB dose dependently reduced cell viability, suppressed cell proliferation, and triggered caspase-mediated apoptosis. Transcriptomic profiling of PAB-treated tumor cells revealed significant enrichment of differentially expressed genes in pathways such as gap junction, cell cycle, and cellular senescence. Mechanistically, CDK1 suppression by PAB, achieved through binding that diminishes its expression and stability, induced G2/M phase arrest and halted mitotic progression. While these findings suggest the potential of PAB as a candidate for canine mammary tumor treatment, further investigations are warranted to delineate its precise in vivo targeting specificity and pharmacodynamic interactions.Discussion: These findings not only expand the translational applicability of PAB in veterinary oncology but also identify CDK1 as a potential therapeutic vulnerability for combinatorial treatment strategies in CMTs.
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DOI
PubMed
高影响因子
Pharmaceutics
·
2019
·Vol. 11
·期 3
·123
·
IF 4.773
Jun Ding,Guilin Chen,Guofang Chen,Mingquan Guo
Epirubicin-capped silver nanoparticles (NPs) were synthesized through a one-pot method by using epirubicin as both the functional drug and the reducing agent of Ag+to Ag0. The preparation process was accomplished in 1 h. In addition, the obtained epirubicin-capped silver nanoparticle was characterized by transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX), and infrared spectroscopy. The results showed that a layer of polymer epirubicin had formed around the silver nanoparticle, which was 30-40 nm in diameter. We further investigated the antitumor activity of the prepared epirubicin-capped silver nanoparticle, and the half maximal inhibitory concentration (IC50) against Hep G2 cells was 1.92 μg/mL, indicating a good antitumor property of the nanoparticle at low dosage.Keywords:epirubicin;one-pot synthesis;silver nanoparticle;antitumor
研究领域:
药学
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纳米医学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF INORGANIC BIOCHEMISTRY
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2020
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IF 3.212
Ying Wang,Qianqian Han,Feng Bai,Qiang Luo,Mingliang Wu,Gang Song,Hongmei Zhang,Yanqing Wang
In this work, the new polysaccharide-platinum conjugates of 5-aminosalicylic acid modified lycium barbarum polysaccharide linking platinum compounds were designed in order to construct an anticancer metal drug delivery system. The multiple analysis methods were used to describe the chemical structure and physical properties of the polysaccharide-metal conjugates . The results showed that 5-aminosalicylic acid successfully acted as linker which was covalently bound between polysaccharide and platinum compound. The morphology and rheological properties of polysaccharide have been changed by the formation of conjugates, which exhibited certain inhibition specificity to A549 (human lung cancer cell line). The agarose gel electrophoresis and fluorescence microscopy results demonstrated that such conjugates promoted the unwinding of DNA and could significantly damage the nucleus of A549 cells. Cell cycle analyzing the Pt complex of conjugates could cause intracellular DNA damage and induced G2 phase arrest . So, polysaccharide-platinum conjugates might find a range of applications, for example in metal anticancer drug delivery.
研究领域:
药理学
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肿瘤学
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生物化学
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产品关联
DOI
PubMed
高影响因子
Chemical Biology & Drug Design
·
2023
·Vol. 102
·期 1
·101-114
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IF 3
Meiya Mao,Xiaojiao Zheng,Yuehua Sheng,Jinghan Chai,Huiqing Ding
Evodiamine (EVO) has been demonstrated to promote apoptosis of ovarian cancer cells, and upregulate miR-152-3p level in colorectal cancer. Here, we explore part of the network mechanism of EVO and miR-152-3p in ovarian cancer. The bioinformatics website, dual luciferase reporter assay, and quantitative real-time polymerase chain reaction were applied to analyze the network among EVO, lncRNA, miR-152-3p, and mRNA. The effect and mechanism of EVO on ovarian cancer cells were determined using cell counting kit-8, flow cytometry, TUNEL, Western blot, and rescue experiments. As a result, EVO dose-dependently attenuated cell viability, induced G2/M phase arrest and apoptosis, promoted miR-152-3p level (4.5- or 2-fold changes), and inhibited expressions of NEAT1 (0.225- or 0.367-fold changes), CDK8 (0.625- or 0.571-fold changes), and CDK19 (0.25- or 0.147-fold changes) in OVCAR-3 and SKOV-3 cells. In addition, EVO decreased Bcl-2 expression, but increased the expressions of Bax and c-caspase-3. NEAT1 targeted miR-152-3p which bound to CDK19. The impacts of EVO on cell viability, cycle, apoptosis, and apoptosis-related proteins were partially reversed by miR-152-3p inhibitor, NEAT1 overexpression, or CDK19 overexpression. Furthermore, miR-152-3p mimic offset the effects of NEAT1 or CDK19 overexpression. The role of NEAT1 overexpression in the biological phenotype of ovarian cancer cells was counteracted by shCDK19. In conclusion, EVO attenuates ovarian cancer cell progression via the NEAT1-miR-152-3p-CDK19 axis.
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2025
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IF 4.7
Hafiz Muhammad Bilal Akram,Yulin Liu,Jianshu Dong,Xueke Zhao,Lidong Wang,Wen Zhao,Hongmin Liu,Liying Ma,Cong Han
Esophageal cancer has been regarded as a serious malignancy due to its poor prognosis and high mortality rate. Serine hydroxymethyltransferase 2 (SHMT2) is emerging as an attractive target for esophageal cancer therapy. Compound W478 was identified as a potent SHMT2 inhibitor with an IC 50 value of 1.21 μM, especially whose chemical structure is distinct from the reported SHMT2 inhibitors. Both cellular thermal shift assay and isothermal titration calorimetry experiments showed that compound W478 tightly bound to SHMT2 (K D = 10.6 ± 1.2 μM). The molecular docking analysis revealed its binding at the folate binding site of SHMT2. Moreover, compound W478 exhibited a significant antiproliferative effect on human esophageal cancer cell lines, KYSE-450 and KYSE-70 cells (IC 50 = 1.62 μM, 1.18 μM, respectively). The wound healing and transwell assays showed that compound W478 could inhibit the migratory and invasive potential of KYSE-450 and KYSE-70 cells in a dose-dependent manner. Further studies demonstrated that compound W478 could induce cell arrest at the G2/M phase and promote cell apoptosis and ROS production in KYSE-450 and KYSE-70 cells. These findings indicated that compound W478 could serve as a promising lead compound for the development of SHMT2 inhibitor to address esophageal carcinoma.
研究领域:
肿瘤学
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分子生物学
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药物化学
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转化医学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
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2022
·
IF 5.168
Yudong Yin,Li Sun,Lixin Sheng,Liqiong Zhang,Jingjing Liu,Xiaoan Wen,Weibin Mo,Quande Wang,Keguang Cheng
In order to discover more effective and less toxic drugs in the field of anti-tumor, the backbone structure of 17 β -estradiol was modified, and 11 target compounds were synthesized. Compounds 5 and 10 , which exhibited better anti-tumor activity and higher selectivity (more than 10-fold), were chosen for further biological investigation. Flow cytometry results indicated that 5 and 10 could arrest MCF-7 cells in the G2 phase and induce apoptosis . Immunohistochemical analysis revealed that 5 and 10 could bind to the estradiol receptor alpha in MCF-7 cells. Western blotting and real-time PCR assays were performed to detect the effects of compounds on apoptosis-related targets at the protein and gene levels. These results showed that both 5 and 10 could dosed-dependently increase the expression of Apaf-1, Bax, caspase-3,8,9 and reduce the expression levels of the anti-apoptotic factors Bcl-2 and Bcl-xL. Besides, the Human apoptosis array assay demonstrated the expression level of death receptor Trail R2/DR5 was upregulated obviously while the expression of TNF R1, IAPs and Hsp27/60/70 were downregulated. On the whole, 5 induced MCF-7 cell death through the endogenous pathway in mitochondria and the exogenous pathway with death receptor Trail R2/DR5.
研究领域:
肿瘤学
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药理学
·
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
Nutrients
·
2021
·Vol. 13
·期 12
·4379
·
IF 5.719
Hui Zhou,Yuanyuan Wu,Eunhye Kim,Haibo Pan,Puming He,Bo Li,Yi Charlie Chen,Youying Tu
Theaflavin-3,3′-digallate (TF3) is the most important theaflavin monomer in black tea. TF3 was proved to reduce blood glucose level in mice and rats. However, the elaborate anti-diabetic mechanism was not well elucidated. In this work, human hepatoma G2 (HepG2) cells and zebrafish (Danio rerio) were used simultaneously to reveal anti-diabetic effect of TF3. The results showed that TF3 could effectively rise glucose absorption capacity in insulin-resistant HepG2 cells and regulate glucose level in diabetic zebrafish. The hypoglycemic effect was mediated through down-regulating phosphoenolpyruvate carboxykinase and up-regulating glucokinase. More importantly, TF3 could significantly improve β cells regeneration in diabetic zebrafish at low concentrations (5 μg/mL and 10 μg/mL), which meant TF3 had a strong anti-diabetic effect. Obviously, this work provided the potential benefit of TF3 on hypoglycemic effect, regulating glucose metabolism enzymes, and protecting β cells. TF3 might be a promising agent for combating diabetes.Keywords:theaflavin-3,3′-digallate;anti-diabetic effect;HepG2 cells;diabetic zebrafish model;glucose metabolism enzymes
研究领域:
生物化学
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医学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Open Access Rheumatology-Research and Reviews
·
2024
·
IF 1.7
Le-Ying Ni,Cheng-Biao Ding,Ji-Min Deng,Zheng-Wei Wu,Yun Zhou
Background Rheumatoid arthritis fibroblast-like synovial cells (RA-FLS) have become the core effector cells for the progression of rheumatoid arthritis due to their “tumor-like cell” characteristics, such as being able to break free from growth restrictions caused by contact inhibition, promoting angiogenesis, invading surrounding tissues, and leading to uncontrolled synovial growth. In recent years, cold air plasma (CAP) has been widely recognized for its clear anticancer effect. Inspired by this, this study investigated the inhibitory effect of CAP on the tumor-like biological behavior of RA-FLS through in vitro experiments.Methods Treatment of RA-FLS with CAP at different time doses (0s, 30s, 60s, 120s). 5-ethynyl-2’-deoxyuridine (EdU) proliferation assay was used to determine the cell viability. Analysis of cell migration and invasion was performed by wound-healing assay, transwell assay and immunofluorescent staining for f-actin, respectively. Flow cytometry technique was used for analysis of cell cycle and determination of reactive oxygen species (ROS). Hoechst staining was used for analysis of cell apoptosis. Protein expression was analyzed by Western blot analysis.Results Molecular and cellular level mechanisms have revealed that CAP blocks RA-FLS in the G2/M phase by increasing intracellular reactive oxygen species (ROS), leading to increased apoptosis and significantly reduced migration and invasion ability of RA-FLS.Conclusion Overall, CAP has significant anti proliferative, migratory, and invasive effects on RA-FLS. This study reveals a new targeted treatment strategy for RA.
研究领域:
风湿病学
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等离子体医学
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细胞生物学
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炎症性疾病
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癌症生物学
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DOI
高影响因子
危险品化学品经营许可证（带存储）