ACS Chemical Neuroscience
·
2023
·
IF 5
Xiaoyi Shi,Meng Li,Qiming Huang,Liuming Xie,Zhibing Huang
Monacolin K (MK), a polyketo secondary metabolic compound of the mold genus Monascus, can promote the apoptosis of malignant cancer cells, possessing potential antitumor properties. However, its mechanism of action on gliomas remains unclear. Here, we explored and investigated the potential of the monacolin K’s antitumor effect on human glioma U251 cells and its possible molecular mechanism. Results showed that the application of 10 μM monacolin K inhibited the proliferation of U251 cells, with an inhibitory rate of up to 53.4%. Additionally, monacolin K induced the generation of reactive oxygen species and activated mitochondria-mediated pathways, including decreased MMP, activation of caspase3/caspase9, decreased Na+/K+-ATPase and Ca2+-ATPase activities, and disruption of the antioxidant system, resulting in the disruption of intracellular reduction–oxidation homeostasis. Monacolin K also activated MAPK and NF-κB pathways, upregulating P38 activity and downregulating JNK/ERK/P65/IκBα expression, ultimately leading to apoptosis of U251 cells. Importantly, monacolin K was not cytotoxic to normal human cells, hUC-MSCs. We concluded that monacolin K can induce apoptosis in U251 cells by triggering ROS-mediated oxidative damage and regulating MAPKs and NF-κB pathways.
研究领域:
肿瘤学
·
细胞生物学
·
药理学
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产品关联
DOI
PubMed
高影响因子
Tomography
·
2017
·Vol. 3
·期 1
·1-8
·
IF 0
E. Mark Haacke
A unique hybrid protein ferritin–enhanced green fluorescent protein (EGFP) was built to serve as an endogenous dual reporter for both fluorescence and magnetic resonance imaging (MRI). It consists of a human ferritin heavy chain (an iron-storage protein) at the N terminus, a flexible polypeptide in the middle as a linker, and an EGFP at the C terminus. Through antibiotic screening, we established stable human glioma U251 cell strains that expressed ferritin–EGFP under the control of tetracycline. These cells emitted bright green fluorescence and were easily detected by a fluorescent microscope. Ferritin–EGFP overexpression proved effective in triggering obvious intracellular iron accumulation as shown by Prussian blue staining and by MRI. Further, we found that ferritin–EGFP overexpression did not cause proliferation differences between experimental and control group cells when ferritin–EGFP was expressed for <96 hours. Application of this novel ferritin–EGFP chimera has a promising future for combined optical and MRI approaches to study in vivo imaging at a cellular level.
研究领域:
医学影像学
·
分子生物学
·
神经科学
·
癌症研究
✓ 已验证
DOI
PubMed
IUBMB LIFE
·
2020
·Vol. 73
·期 2
·398-407
·
IF 3.244
Zhou Jing,Minghe Li,Hongyuan Wang,Zhuo Yang,Shaolong Zhou,Jian Ma,Enping Meng,Hengwei Zhang,Wulong Liang,Weihua Hu,Xinjun Wang,Xudong Fu
Glioblastoma multiforme (GBM) is among the most common adult brain tumors with invariably fatal character. Following the limited conventional therapies, almost all patients, however, presented with symptoms at the time of recurrence. It is dire to develop novel therapeutic strategies to improve the current treatment of GBM. Gallic acid is a well-established antioxidant, presenting a promising new selective anti-cancer drug, while gold nanoparticles (GNPs) can be developed as versatile nontoxic carriers for anti-cancer drug delivery. Here, we prepared gallic acid-GNPs (GA-GNPs) by loading gallic acid onto GNPs, reduction products of tetrachloroauric acid by sodium citrate, through physical and agitation adsorption. GA-GNPs, rather than GNPs alone, significantly inhibited the survival of U251 GBM cells, as well as enhanced radiation-induced cell death. Moreover, GA-GNPs plus radiation arrested the cell cycle of U251 at the S and G2/M phases and triggered apoptotic cell death, which is supported by increased BAX protein levels and decreased expression of BCL-2. Thus, GA-GNPs have great potential in the combination with radiation therapy in future studies for GBM treatment.
研究领域:
肿瘤学
·
纳米技术
·
放射治疗
✓ 已验证
DOI
PubMed
高影响因子
VIROLOGICA SINICA
·
2012
·Vol. 27
·期 1
·19-25
·
IF 0
Liang Yuan-Yuan,Wang Bin,Qian Dong-Meng,Li Ling,Wang Zhi-Hao,Hu Ming,Song Xu-Xia
To investigate the inhibitory effects of Ginsenoside Rb1 (GRb1) on apoptosis caused by Herpes Simplex Virus-1(HSV-1) in Human Glioma Cells (U251), U251 cells were infected by HSV-1 at a multiplicity of infection of 5 and GRb1, GRb1+HSV-1, HSV-1 and control groups. MTT and cell apoptosis assays were used to detect the inhibitory effects of GRb1 on the apoptosis of U251 cells that caused by HSV-1 infection for various concentrations of drug and virus treatments by MTT assay. We found that in the 400 μg/mL GRb1 and 400 μg/mL GRb1+HSV-1 groups, MTT values were higher than control group at all times ( P <0. 05). Moreover, the apoptosis rate in the 400 μg/mL GRb1+HSV-1 group was lower than the HSV-1 group ( P <0. 05). These results confirmed that, at appropriate concentrations, GRb1 could inhibit nerve cell apoptosis in HSV-1 infections.
研究领域:
医学
·
病毒学
·
神经科学
·
药理学
✓ 已验证
DOI
PubMed
JOURNAL OF CHROMATOGRAPHY A
·
2023
·
IF 4.1
Hao Chi,Sheng Tian,Xiu Li,Yuchu Chen,Qiumin Xu,Qixiao Wang,Wenwan Shi,Michael Adu-Frimpong,Shanshan Tong
In order to improve the separation process of affinity chromatography that has silica as the main carrier material, we sought to construct Lipid [email protected] 4B affinity chromatography model. We extracted the lipid rafts from U251 cells with a descaler method and sucrose density gradient centrifugation. Afterwards, it was discovered via immunofluorescence that the lipid rafts contain a large amount of tropomyosin-related kinase A (TrkA) protein. Also, agarose powder in the lyophilised state was pretreated, before the lipid rafts were coupled to the agarose gel in a coupling buffer of alkaline pH. CNBr-Sepharose 4B affinity gel packing was characterised using UV spectrophotometric, immunofluorescence and scanning electron microscopic techniques, wherein and the results showed that the lipid rafts were successfully coupled to the agarose gels. Three compounds were used to verify the specific sorption of Sepharose 4B and CNBr-Sepharose 4B, which showed no specific sorption on the materials. Of note, the prepared Lipid [email protected] 4B agarose gels packed with TrkA-rich target proteins could be successfully validated for the active drug gefitinib with high affinity sorption efficiency and eluted with good recovery and reproducibility. This study broadens the range of affinity chromatography carrier materials and provides a reference for research in active drug screening.
研究领域:
生物化学
·
药学
·
生物技术
·
分析化学
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产品关联
DOI
PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
·
2023
·Vol. 20
·期 8
·e202300942
·
IF 2.9
Jiayi Ou,Weiyun Tan,Gong Chen,Xianjing Yang,Yan Luo,Xiaobao Jin,Lianbao Ye
Glioma is the most common brain tumor and its treatment options are limited. Abietic acid and dehydroabietic acid are tricyclic diterpenoid oxygen compounds with strong lip solubility and anti-glioma activity. In this study, novel rosin diterpenoid derivatives were designed and synthesized using abietic acid and dehydrogenated abietic acid as lead compounds and their activities against T98G, U87MG, and U251 cells were evaluated by CCK-8 methods. The in vivo activity of compounds with stronger activity in vitro was preliminarily studied through the Zebrafish model. The results showed that the IC 50 values of B6 , B8 , B10 , and B12 were 11.47 to 210.6 μM, which were exhibited higher antiproliferative potency against T98G, U87MG, and U251. The scratch experiment showed that B12 inhibited the migration of T98G in a time-dependent and concentration-dependent manner. The results of in vivo activity further explained that B12 could inhibit the proliferation of the T98G. The pKa values of B6 , B8 , B10 , and B12 were 7.17 to 7.35, which were within the ideal range of glioma drugs. The ADME predictions indicated that these derivatives could pass through the blood-brain barrier. In addition, molecular docking primarily explained interaction between compounds and protein. These results suggested that B12 should be a promising candidate that merits further attention in the development of anti-glioma drugs. Graphical
研究领域:
药理学
·
肿瘤学
·
药物化学
·
药物发现
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2021
·Vol. 47
·期 5
·1-11
·
IF 4.101
Yunsheng Liu,Xiangping Xu,Han Tang,Yuchen Pan,Bing Hu,Guodong Huang
There is a growing evidence that Fyn kinase is upregulated in glioblastoma multiforme (GBM), where it plays a key role in tumor proliferation and invasion. In the present study, the antitumor effects of rosmarinic acid (RA), a Fyn inhibitor, were explored in human‑derived U251 and U343 glioma cell lines. These cells were treated with various concentrations of RA to determine its effects on proliferation, migration, invasion, apoptosis, and gene and protein expression levels. The CCK‑8 assay revealed that RA significantly suppressed cell viability of U251 and U343 cells. Furthermore, RA significantly reduced proliferation rates, inhibited migration and invasion, and decreased the expression levels of invasion‑related factors, such as matrix metalloproteinase (MMP)‑2 and MMP‑9. TUNEL staining revealed that RA resulted in a dose‑dependent increase of U251 and U343 cell apoptosis. In line with this finding, the expression of apoptosis suppressor protein Bcl‑2 was downregulated and that of the pro‑apoptotic proteins Bax and cleaved caspase‑3 was increased. In addition, it was revealed that the phosphatidylinositol 3‑kinase (PI3K)/Akt/nuclear factor‑κB (NF‑κB) signaling pathway was involved in RA‑induced cytotoxicity in U251 and U343 cells. Collectively, the present study suggested RA as a drug candidate for the treatment of GBM.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 107
·105661-105675
·
IF 3.289
Xueqin Wang,Yanyan Chang,Dongxu Zhang,Baoming Tian,Yan Yang,Fang Wei
A combinatorial nanosystem with the advantages of superparamagnetic iron oxide nanoparticles (SPIO NPs) and targeting polymer carriers is expected to improve the therapeutic effects in developing multifunctional delivery systems. Here we developed an innovative tumor-specific multi-functional SPIO NPs nanoplatform containing the antitumor drug doxorubicin (DOX) and fluorescent dye rhodamine B isothiocyanate (RBITC) for theranostic analysis and anti-tumor therapy in human brain tumor U251 MG cells. The core nanocarrier SPIO NPs (γ-Fe2O3) were synthesized and decorated with chitosan (CS), subsequently followed with conjugation with tumor-specific ligand transferrin (Tf) to fabricate tumor-targeted Tf–CS/SPIO NPs. The anti-tumor drug DOX was then loaded onto Tf–CS/SPIO NPs, and transferred into U251 MG cells for assaying their biological effects. Besides, the produced Tf–CS/SPIO NPs were fluorescently labeled with RBITC for simultaneously intracellular fluorescent/magnetic resonance imaging in targeted U251 MG cells. The results showed that the fabricated Tf–CS/SPIO NPs nanocarriers demonstrated some favorable properties, including immediate responses under magnetic fields, stable behavior in different media, efficient encapsulation for drug loading, undetectable cytotoxicity, and effective intracellular visualization. Moreover, the fluorescent Tf–CS/SPIO NPs could be successfully applied for concurrent fluorescent/magnetic resonance imaging, and the finalized drug-loading Tf–CS/SPIO NPs displayed an improved cellular uptake, and thus effectively killed tumor cells through inducing a concurrence of cell apoptosis and autophagy in the treated tumor U251 cells. Therefore, the fabricated Tf–CS/SPIO NPs should be of great significance in developing multi-purpose nanocarriers for anti-tumor drug delivery and fluorescent/magnetic resonance imaging in human brain tumor treatments.
研究领域:
纳米技术
·
药学
·
生物医学工程
·
癌症研究
·
分子成像
✓ 已验证
DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-18
·
IF 10.6
Jiang Hanwen,Sun Jingxian,Liu Fucong,Zhao Yuanjiao,Chen Xin,Dai Changsong,Wen Zhaohui
Background Photodynamic therapy (PDT) efficacy of bismuth sulfide (Bi 2 S 3 ) semiconductor has been severely restricted by its electron–hole pairs (e − −h + ) separation inefficiency and oxygen (O 2 ) deficiency in tumors, which greatly hinders reactive oxygen species (ROS) generation and further clinical application of Bi 2 S 3 nanoparticles (NPs) in biomedicine. Results Herein, novel Bi 2 S 3 /titanium carbide (Ti 3 C 2 ) two-dimensional nano-heterostructures (NHs) are designed to realize multimode PDT of synchronous O 2 self-supply and ROS generation combined with highly efficient photothermal tumor elimination for hypoxic tumor therapy. Bi 2 S 3 /Ti 3 C 2 NHs were synthesized via the in situ synthesis method starting from Ti 3 C 2 nanosheets (NSs), a classical type of MXene nanostructure. Compared to simple Bi 2 S 3 NPs, Bi 2 S 3 /Ti 3 C 2 NHs significantly extend the absorption to the near-infrared (NIR) region and enhance the photocatalytic activity owing to the improved photogenerated carrier separation, where the hole on the valence band (VB) of Bi 2 S 3 can react with water to supply O 2 for the electron on the Ti 3 C 2 NSs to generate ·O 2 − and ·OH through electron transfer. Furthermore, they also achieve 1 O 2 generation through energy transfer due to O 2 self-supply. After the modification of triphenylphosphium bromide (TPP) on Bi 2 S 3 /Ti 3 C 2 NHs, systematic in vitro and in vivo evaluations were conducted, revealing that the synergistic-therapeutic outcome of this nanoplatform enables complete eradication of the U251 tumors without recurrence by NIR laser irradiation, and it can be used for computed tomography (CT) imaging because of the strong X-ray attenuation ability. Conclusion This work expands the phototherapeutic effect of Bi 2 S 3 -based nanoplatforms, providing a new strategy for hypoxic tumor theranostics.
研究领域:
纳米技术
·
生物医学工程
·
癌症治疗
·
材料科学
·
光疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Zhipeng Yang,Haoyuan Li,Biao Yang,Yanjie Liu
Glioblastoma (GBM) is the most common and aggressive malignant brain tumor. Standard therapy includes maximal surgical resection, radiotherapy, and adjuvant temozolomide (TMZ) administration. However, the rapid development of TMZ resistance and the impermeability of the blood–brain barrier (BBB) significantly hinder the therapeutic efficacy. Herein, we developed spatiotemporally controlled microneedle patches (BMNs) loaded with TMZ and niclosamide (NIC) to overcome GBM resistance. We found that hyaluronic acid (HA) increased the viscosity of bovine serum albumin (BSA) and evidenced that concentrations of BSA/HA exert an impact degradation rates exposure to high-temperature treatment, showing that the higher BSA/HA concentrations result in slower drug release. To optimize drug release rates and ensure synergistic antitumor effects, a 15% BSA/HA solution constituting the bottoms of BMNs was chosen to load TMZ, showing sustained drug release for over 28 days, guaranteeing long-term DNA damage in TMZ-resistant cells (U251-TR). Needle tips made from 10% BSA/HA solution loaded with NIC released the drug within 14 days, enhancing TMZ’s efficacy by inhibiting the activity of O6-methylguanine-DNA methyltransferase (MGMT). BMNs exhibit superior mechanical properties, bypass the BBB, and gradually release the drug into the tumor periphery, thus significantly inhibiting tumor proliferation and expanding median survival in mice. The on-demand delivery of BMNs patches shows a strong translational potential for clinical applications, particularly in synergistic GBM treatment.
研究领域:
肿瘤学
·
药学
·
神经科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL SYSTEMATICS AND ECOLOGY
·
2023
·
IF 1.6
Dongyu Gu,Chen Fang,Jing Liu,Zhongai Jiang,Gang Li,Minjing Li,Min Zhang,Yun Huang
Salicornia europaea L. is an economic plant which can grow in saline-alkali land, beach and other heavy saline soil . In this study, the inhibitory activities of S. europaea extracts against tumor cell growth including human non-small cell lung cancer cell A549 , human liver cancer cell HepG2, and brain glioma cell U251 were screened. The results showed that the ethanol extract of S. europaea had an inhibitory effect on the proliferation of A549 cells, and the inhibition of tumor cells showed time-dose relationship. Moreover, the ethanol extract of S. europaea was extracted and fractionated with different organic solvents and the activity results indicated that the petroleum ether fraction with IC 50 of 96.5 μg mL −1 possessed the best activity against A549 cells. Then seven compounds, including 30-norhederagenin ( 1 ), 24-methylenecycoartanol ( 2 ), pheophorbide A ( 3 ), stigmasterol ( 4 ), β -sitosterol ( 5 ), α-spinasterol ( 6 ), phytol ( 7 ) were isolated and identified from the petroleum ether fraction of S. europaea . Besides, the oil obtained from the petroleum ether fraction was analyzed by GC-MS, and fourteen compounds were identified. The compounds identified from the petroleum ether fraction mainly consisted of triterpenes , sterols, fatty acids, and their lipids .
研究领域:
药理学
·
植物科学
·
癌症研究
·
生物化学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）