International Journal of Clinical and Experimental Pathology
·
2015
·
IF 1.891
Shupeng Zhao,Haigang Chang,Pengju Ma,Guojun Gao,Cailing Jin,Xinli Zhao,Wenke Zhou,Baozhe Jin
Objective: To investigate the effect of isoliquiritigenin on the activity of DNA topoisomerase (TOP I) and its inhibitory effect on the growth of U87 glioma cells. Methods: This study investigated the inhibitory effect of isoliquiritigenin on the growth of U87 glioma cells and its cytotoxicity by MTT method and determined the effect of isoliquiritigenin on TOP I activity by agarose gel electrophoresis. On this basis, we studied the interaction between isoliquiritigenin and TOP I and DNA. Finally, we further discussed the effect of isoliquiritigenin on the activity of Caspase 3, the apoptosis protein of U87 glioma cells. Results: Isoliquiritigenin could inhibit the growth of U87 glioma cells (half inhibitory concentration IC50: 0.221 mM) and is of low cytotoxicity to normal cells. Agarose gel electrophoresis showed that isoliquiritigenin had significant inhibitory effect on TOP I activity. Molecular simulation results indicated that isoliquiritigenin took priority of binding to the active center of TOP I, and formed hydrogen bonds with the catalytic site Try723. Finally, Caspase 3 activity detection results suggested that isoliquiritigenin could significantly increase the activity of Caspase 3 (P < 0.05). Conclusion: Isoliquiritigenin had a reversible inhibitory effect on TOP I activity, reduced the rate of single strand DNA unwinding in tumor cells, and thus played an important role in inducing the apoptosis of U87 glioma cells.
研究领域:
肿瘤学
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分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOINORGANIC CHEMISTRY AND APPLICATIONS
·
2023
·
IF 3.8
P. Baby Shakila,Abdurahman Hajinur Hirad,Abdullah A. Alarfaj,Samer Hasan Hussein-Al-Ali,Beza Mulugeta
Multiple chemodrugs with nanotechnology have proven to be an effective cancer treatment technique. When taken combined, cabazitaxel (CTX) and cisplatin (PT) have more excellent cytotoxic effects than drugs used alone in the chemotherapy of several different cancers. However, several severe side effects are associated with using these chemotherapy drugs in cancer patients. Gold nanomaterials (AuNMs) are promising as drug carriers because of their small diameter, easy surface modifications, good biocompatibility, and strong cell penetration. This work aimed to determine the CTX and PT encapsulated with AuNMs against human glioma U87 cancer cells. The fabrication of the AuNMs achieved a negative surface charge, polydispersity index, and the mean sizes. The combined cytotoxic effect of CTX and PT bound to AuNMs was greater than that of either drug alone when tested on U87 cells. The half inhibitory concentration (IC50) values for free PT were 54.7 μg/mL (at 24 h) and 4.8 g μg/mL (at 72 h). Results acquired from the MTT assay show cell growth decreases time- and concentration-dependent AuNMs, free CTX, free PT, and AuNMs@CTX/PT-induced cytotoxicity and, ultimately, the cell death of U87 cells via apoptosis. The biochemical apoptosis staining techniques investigated the cells’ morphological changes of the cells (acridine orange and ethidium bromide (AO-EB) and nuclear staining (DAPI) techniques). The AO-EB and nuclear staining results reveal that the NPs effectively killed cancer cells. Furthermore, the flow cytometry analysis examined the mode of cell death. Therefore, AuNMs@CTX/PT has excellent potential in the cancer therapy of different cancer cells.
研究领域:
肿瘤学
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纳米医学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2020
·
IF 5.162
Yue Shi,Xiao Wang,Ning Wang,Fei-Fei Li,Yu-Lin You,Shu-Qi Wang
Glioblastoma (GBM) is the most malignant central nervous system tumor, with poor prognosis. Temozolomide (TMZ) has been used as a first–line drug for the treatment of GBM for over a decade, but its treatment benefits are limited by acquired resistance. Polysaccharides from Cibotium barometz (CBPs) are polysaccharides purified from the root of Cibotium barometz (L.) J . Sm., possessing sensitizing activity. The purpose of this study was to investigate the anti–cancer effect of CBP from different processing methods on U87 cells using a 1 H NMR–based metabolic approach, complemented with qRT–PCR and flow cytometry, to identify potential markers and discover the targets to explore the underlying mechanism. Cibotium barometz is usually processed under sand heating in clinical applications. Polysaccharides from both the processed (PCBP) and raw (RCBP) C. barometz were prepared, and the effect on enhancing the sensitivity to TMZ was investigated in vitro. CBP can significantly increase the toxicity of TMZ to the U87 cell line, promote apoptosis, enhance cell cycle changes, and arrest cells in S phase, and RCBP demonstrated better activity. Multivariate statistical analyses, such as principal component analysis (PCA) and orthogonal projection to latent structure with discriminant analysis (OPLS–DA), were used to identify metabolic biomarkers, and 12 metabolites in the cell extract samples were clearly identified as altered after RCBP exposure. NMR–based cell metabolomics provided a holistic method for the identification of CBP's apoptosis–enhancing mechanisms and the exploration of its potential applications in preclinical and clinical studies.
研究领域:
肿瘤学
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药理学
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代谢组学
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生物医学研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2016
·Vol. 37
·期 4
·998-1004
·
IF 2.348
Yang Li,Zhenqing Wei,Bin Dong,Zhigang Lian,Yinghui Xu
Phosphoglucose isomerase/autocrine motility factor (PGI/AMF) is secreted by tumors and influences tumor growth and metastasis. In order to investigate the effects of silencing PGI/AMF on the migration and the sphere forming abilities of human glioblastoma U87 cells, as well as on the side population cells (SPCs), PGI/AMF was silenced using siRNA. Western blot analysis and RT-qPCR were used to assess the expression of PGI/AMF, Akt and SRY (sex determining region Y)-box 2 (SOX2). Wound healing, migration and tumorsphere formation assays were performed to assess invasion and metastatic potential. The proportion of SPCs was determined using Hoechst 33342 dye and flow cytometric analysis. PGI/AMF silencing inhibited the wound healing capacity and migration ability of U87 cells by 52.6 and 80.4%, respectively, compared with the scrambled siRNA (both P<0.001). Silencing of PGI/AMF decreased the proportion of SPCs in the U87 cells by 80.9% (P<0.01). The silencing of PGI/AMF decreased the number and size of tumorspheres by 53.1 and 39.9%, respectively, compared with the scrambled siRNA (both P<0.01). The silencing of PGI/AMF decreased the levels of phosphorylated Akt (-71.9%, P<0.001) compared with the scrambled siRNA, as well as the levels of the stemness marker, SOX2 (-61.7%, P<0.01). Taken together, these findings suggest that PGI/AMF silencing decreases migration, tumorsphere formation as well as the proportion of SPCs in glioblastoma U87 cells. We suggest that the Akt pathway is involved, and our results provide a potential new target for the treatment of glioblastoma.
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
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 104
·101790-101799
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IF 3.289
Lijun Kong,Zezhong Mu,Yuan Yu,Lixia Zhang,Jinxia Hu
Targeted delivery of therapeutic drugs into cancer cells is a facile method to improve therapeutic efficacy. Focused on this point, a functionalized porous hydroxyapatite (HAp) nanoparticle-based nanocarrier consisting of polyethyleneimine (PEI) coating and outer hyaluronic acid (HA) modification (HAp–PEI–HA) has been developed. In this nanocarrier, PEI was coated onto the HAp to stabilize the nanoparticles, and HA acted as an efficient targeting ligand to selectively bind the CD44 receptors which are overexpressed on the surface of some cancer cells. Various techniques demonstrated the successful preparation of the HAp–PEI–HA nanoparticles. The resulting HAp–PEI–HA nanoparticles showed better dispersibility and stability in aqueous solution compared to bare HAp. In addition, the DOX released from DOX@HAp–PEI–HA exhibited a pH-responsive release profile. The targeting property of HAp–PEI–HA was investigated on A549 cells with high CD44 receptor expression and U87 cells with low CD44 receptor expression. The result showed enhanced cellular uptake of HAp–PEI–HA nanoparticles in A549 cells through CD44 receptor mediated cellular endocytosis. Furthermore, the effective targeted delivery of DOX by HAp–PEI–HA in A549 cells led to enhanced therapeutic efficacy. Thus, the designed HAp–PEI–HA nanocarrier showed promising potential for targeted drug delivery in cancer therapy.
研究领域:
纳米技术
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药剂学
·
癌症研究
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生物材料科学
✓ 已验证
产品关联
DOI
高影响因子
RSC Advances
·
2019
·Vol. 9
·期 11
·6003-6010
·
IF 3.049
Xian-Ling Yang,Xiu Xing,Jun Li,Yan-Hong Liu,Na Wang,Xiao-Qi Yu
Although functional aliphatic polycarbonates (APCs) have attracted prominent research interest as stimuli-responsive biomaterials, the majority of functional APCs are fabricated by detrimental organometallic catalysts or organo-catalysts. Herein, a facile synthetic strategy based on enzymatic polymerization was developed to construct a selenium-containing amphiphilic aliphatic polycarbonate (mPEG-b-CMP45). Specifically, the selenium in its backbone framework underwent a hydrophobic–hydrophilic transition upon exposure to the abnormal ROS level of the tumor, thus providing a promising platform for ROS-triggered drug release. This amphiphilic mPEG-b-CMP45 efficiently encapsulated doxorubicin (DOX) via self-assembly in aqueous solution and showed an excellent ability to regulate the release of DOX in response to H2O2 at biologically relevant concentrations (100 μM). These DOX-loaded nanoparticles could easily be internalized into U87 cells and possess the inherent antitumor properties of DOX, while they exhibited much lower cytotoxicity in normal cells HL-7702. Moreover, in many cases, the introduction of selenium caused high cytotoxicity of the materials, but the cytotoxicity results in HL-7702 cells demonstrated the good biocompatibility of mPEG-b-CMP45. These collective data suggested the potential use of mPEG-b-CMP45 as a biocompatible and smart drug delivery vehicle.
研究领域:
材料科学
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药剂学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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