Acta Pharmaceutica Sinica B
·
2025
·
IF 14.6
Fangfei Li,Zhaoxin Zhang,Qinyan Shi,Rubing Wang,Ming Ji,Xiaoguang Chen,Yong Li,Yunbao Liu,Shishan Yu
Glioma is difficult to treat due to the unique tumor microenvironment and blood-brain barrier. (13a S )-3-Hydroxyl-6,7-dimethoxyphenanthro[9,10- b ] indolizidine (PF403), a phenanthroindolizidine alkaloid, has been identified as a promising therapeutic agent for the treatment of glioma. However, the anti-glioma mechanism of PF403 in vivo has not been conclusively verified and must be further elucidated. Hence, a strategy without chemical modification was applied to identify the target of PF403. In this study, we identified nicotinamide phosphoribosyl transferase (NAMPT) as the target of PF403 by using thermal proteome profiling (TPP). Moreover, microscale thermophoresis (MST), surface plasmon resonance (SPR), and isothermal titration calorimetry (ITC) experiments confirmed that NAMPT exhibits good affinity for PF403. Direct and indirect enzyme activity assays revealed that PF403 inhibited the catalytic activity of NAMPT, leading to a decrease in the concentration of nicotinamide adenine dinucleotide (NAD + ) in U87 cells. X-ray diffraction and amino acid spot mutation experiments revealed that PF403 primarily relies on the formation of pi–pi interactions with residue Tyr188 to maintain binding with NAMPT (PDB code 8Y55). After NAMPT was knocked down with lentivirus, PF403 lost or partially lost its antitumor activity at the cellular and animal levels. These findings suggest that PF403 exerts antitumor activity by directly targeting NAMPT.
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
·
2023
·Vol. 396
·期 6
·1247-1255
·
IF 3.6
Su Jie,Yin Wei,Huo Mengmeng,Yao Qing,Ding Liqiong
Glioma is an extremely aggressive primary brain tumor, which is highly resistant to chemotherapy, presenting a therapeutic challenge. Here, we explored the anti-glioma effects and the underlying mechanism of lycorine, an isoquinoline alkaloid isolated from lycoris on glioma cells. We found that lycorine could dose dependently inhibit C6 glioma cell growth and induce cell apoptosis and intracellular reactive oxygen species (ROS) production. The half-maximal inhibitory concentration (IC 50 ) values of lycorine on C6 glioma cells at 48 h was 2.85 μM. Meanwhile, lycorine treatment caused dysfunction of the NF-κB signal, as demonstrated by the up-regulation of NF-κB inhibitor protein IκB and the downregulation of the NF-κB phosphorylation protein p-p65. The addition of NF-κB inhibitor SC75741 further confirmed the importance of the NF-κB pathway in lycorine-induced cell-growth inhibition. Moreover, lycorine might act synergically with temozolomide (TMZ) to reduce drug resistance by blocking the NF-κB pathway. Our study suggested that lycorine exerts an anti-glioma effect by inducing ROS production and inhibiting NF-κB, which validated that lycorine may be a potential candidate for glioma treatment alone or in combination with TMZ.
研究领域:
肿瘤学
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药理学
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细胞生物学
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神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Ming Zhao,Mengnan Zhao,Chen Fu,Yang Yu,Ailing Fu
Background Glioma is the most aggressive and lethal brain tumor in humans, it comprises about 30 per cent of all brain tumors and central nervous system tumors.Purpose The objective of this study was to create novel brain-targeting nanoliposomes to encapsulate curcumin as a promising option for glioma therapy.Patients and methods Human glioma cells (U251MG) were used to determine cell uptake efficiency and possible internalization mechanism of the curcumin-loaded nanoliposomes modified by a brain-targeting peptide RDP. In addition, intracranial glioma mice model was prepared by transplantation of U251MG cells into the mice striatum, and then the liposomes were intravenously administered into the glioma-bearing mice to evaluate the anti-glioma activity.Results RDP-modified liposomes (RCL) could enter the brain and glioma region, and were internalized by the glioma cells perhaps through acetylcholine receptor-mediated endocytosis pathway. Furthermore, the RCL prolonged the survival time of the glioma-bearing mice from 23 to 33 days, and the inhibition mechanism of the RCL on glioma cell was partly due to cell cycle arrest at the S phase and induction of cell apoptosis.Conclusion This study would provide a potential approach for targeted delivery of drug-loaded liposomes for glioma treatment.
研究领域:
肿瘤学
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药剂学
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神经科学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Computational Intelligence and Neuroscience
·
2022
·
IF 3.12
Zhihua Chen,Guofeng Zhu,Chunpeng Sheng,Jianwei Lei,Sihui Song,Jianming Zhu
Temozolomide (TMZ), an oral alkylating agent, is the widely used first-line chemotherapeutic reagent for glioma in clinical practice. However, TMZ-induced autophagy is another cellular process favoring glioma cell survival. This study aimed to explore whether hispidulin can facilitate TMZ-induced cell death of glioma. The MTT assay showed that coadministration with hispidulin and TMZ could significantly decrease the viability of glioma U87MG cells. Meanwhile, hispidulin administration was also observed to promote TMZ-induced apoptosis. Furthermore, additional hispidulin treatment further elevated TMZ-induced expression of Bax, cleaved-caspase-9, and cleaved-caspase-3 protein but decreased Bcl-2 protein expression in U87MG cells. We also observed that hispidulin suppressed TMZ-induced autophagy to promote apoptosis, as showed by decreased AVOs and LC3B-I/II protein expression. These results collectively suggested that the combination of hispidulin and TMZ could improve the antitumor efficiency of TMZ against malignant gliomas.
研究领域:
肿瘤学
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药理学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL SCIENCES
·
2020
·
IF 2.997
Na Wang,Wenyuan Zhang,Dandan Hu,Lei Jiang,Xiaoying Liu,Shukun Tang,Xuegang Zhou,Ting Liu,Xuefeng Tang,Yanqun Chai,Minghui Li,Haisheng Peng,Zhimin Du
Glioma is one of the fatal intracranial cancers that is a huge challenge to decrease the death rate currently. The deep penetration and high accumulation of therapeutic inorganic ions into the tumor site are extremely impeded due to the existence of physiological barriers, which limits to widen the indication of some drugs such as arsenic trioxide . The previous data have confirmed that the mannose substrate (MAN) without acetyl groups facilitates vesicles to go into the brain. Given that deacetylation of Ac 4 MAN groups on the surface of liposomes under the enzyme incubation occurred, namely ‘prodrug-like’ features of vesicles, the liposomes could more easily penetrate the BBB , target the glioma site, release arsenic trioxide, and inhibit the growth of glioma cells in the brain. Besides, the possibility of Ac 4 MAN binding to Gluts could be reduced due to the steric hindrance of acetyl groups, decreasing the off-target effects of vesicles. Here, we developed ‘prodrug-like’ arsenic trioxide (As 2 O 3 , ATO)-loaded liposomes inserted with distearoyl phospho-ethanolamine-polyethylene glycol-1000- p -carboxylpheny-α- d -acetylmannosamine (DSPE-PEG-1000-Ac 4 MAN), which was named Ac 4 MAN-ATO-LIP. Cytotoxic experiments of liposomes indicated that the toxicity of Ac 4 MAN-ATO-LIP was lower than that of free ATO but stronger than that of ATO-LIP (without insertion of DSPE-PEG-1000-Ac 4 MAN). The uptake of vesicles by U87 glioma cells displayed that the cellular uptake of Ac 4 MAN-Rho-LIP (labeled by rhodamine) was remarkably improved, compared with Rho-LIP. The in vivo biodistribution results showed the superiority of Ac 4 MAN-Rho-LIP in enhanced intracranial accumulation. Furthermore, the treatment of orthotopic glioma in Balb/c nude mice with Ac 4 MAN-ATO-LIP elongated the survival time of the animals than that with physiological saline, free ATO, or ATO-LIP, respectively. All the results suggested that the Ac 4 MAN-ATO-LIP had stronger anti-glioma effects as well as lower toxicities, and may be a promising approach for the treatment of brain cancer.
研究领域:
药理学
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神经肿瘤学
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药物递送系统
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癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2018
·
IF 3.997
Cihui Tian,Sajid Asghar,Yurui Xu,Zhipeng Chen,Mei Zhang,Lin Huang,Junxiu Ye,Qineng Ping,Yanyu Xiao
In this study, a redox-sensitive glioma-targeting micelle system was designed to deliver curcumin (CUR) by conjugating it to hyaluronic acid (HA-s-s-CUR, HSC) via disulfide linkage. The effect of the molecular weight of HA on the physicochemical characteristics of HSC conjugates and their in vitro effects in glioma cells were also explored. These conjugates formed nano-scale micelles (209–926 nm) independently in aqueous solution. The micelles greatly increased the solubility of CUR and improved its stability, which is crucial for harnessing the therapeutic potential of this active molecule. The redox sensitivities of different HSC micelles were measured by using a dynamic light scattering method and in vitro release assay, which showed that the low (50 kDa) and medium molecular weight (200 kDa and 500 kD) HA-based conjugates were sensitive to GSH, whereas higher molecular weights (1000 kDa and 2000 kDa) did not show redox-sensitivity. Increased cytotoxicity and uptake of low and medium molecular weight-modified HSC conjugates by the glioma cells further confirmed that the sensitive micelles are more effective for intracellular drug delivery compared to the high molecular weight-modified HSC conjugates or the plain CUR . In summary, the molecular weight of HA affects the physicochemical attributes of HSC conjugates. Only HSC micelles made with HA molecules less than 500 kDa exhibit redox sensitivity.
研究领域:
药学
·
生物医学工程
✓ 已验证
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2016
·
IF 3.902
Yi Zhang,Zhongbing Huang,Zhi Wu,Guangfu Yin,Lei Wang,Fabao Gao
Absence of efficient targeting limits the application of magnetic nanochains (NCs) in the diagnosis of early brain cancer. Herein, dextran-coated NCs (more than 100 nm length and ∼10 nm cores diameter), which were modified by cyclic pentapeptide c(RGDyC) or chlorotoxin (CTX) as the targeting molecules, were fabricated via carbodiimide chemistry and thiol technique. The analysis results revealed that the obtained slender NCs exhibited good biocompatibility, superparamagnetic property, high transverse relaxivity ( R 2 ) and longer blood circulation time. The test results of human umbilical vein endothelial cells and U251 human glioma cells indicated that the conjugation of c(RGDyC) could obviously increase the cyto-internalization of c(RGDyC)-NCs, however, CTX modification could significantly enhance accumulation of CTX-NCs in U251 cells, leading to cellular apoptosis. The results of in vivo biodistribution tests and in vivo magnetic resonance (MR) imaging indicated that, although the c(RGDyC)-NCs could target early glioma to some extent and obviously enhance the contrast of MR imaging, CTX-NCs possessed higher tumor-targeting ability and good inhibition effect than the c(RGDyC)-NCs, suggesting that CTX-NCs are promising candidates for the diagnosis and therapy of early glioma.
研究领域:
生物医学工程
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肿瘤学
·
分子影像学
✓ 已验证
DOI
PubMed
高影响因子
ACS Omega
·
2024
·
IF 3.7
Shiqiang Hou,Ning Lin,Yi Wang
Red-emitting fluorescent carbon dots (CDs) have garnered significant attention due to their wide-ranging applications in biological fields. However, challenges such as complex precursors, labor-intensive preparation processes, and low quantum yields have hindered their broader utilization. In this study, we developed a simple and efficient solvothermal method to synthesize fluorescent CDs with tunable emission wavelengths using aniline derivatives as precursors. The emission wavelengths of the synthesized CDs were influenced by the functional groups at the para-position of the aniline derivatives with stronger electron-donating effects leading to a red shift in emissions. Notably, bright red-emitting CDs with a quantum yield of 19.42% and excellent photobleaching resistance were obtained by using p-phenylenediamine as the sole precursor. These CDs exhibited sensitivity to Fe3+ ions, demonstrating a strong linear detection range (R2 = 0.999) from 0 to 50 μM. Additionally, the CDs were uniform in size (2–5 nm), emitted stable red fluorescence in pH conditions ranging from 4 to 10, and were successfully internalized by glioma cells, enabling precise fluorescence imaging of gliomas both in vitro and in vivo.
研究领域:
生物医学工程
·
材料科学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Death & Disease
·
2024
·Vol. 15
·期 11
·1-10
·
IF 8.1
Luo Yusong,Liu Ruolan,Zhang He,Wang Hongyu,Yin Hang,Tian Guopeng,Wang Bo,Yan Yunji,Ding Zilin,Dai Junqiang,Niu Liang,Yuan Guoqiang,Pan Yawen
Glioma is a common primary nervous system malignant tumor with poor overall cure rate and low survival rate, yet successful treatment still remains a challenge. Here, we demonstrated that amantadine (AMT) exhibits the powerful anti-glioma effect by promoting apoptosis and autophagy in vivo and in vitro. Mechanistically, amantadine induces a large amount of reactive oxygen species (ROS) accumulation in glioma cells, and then triggers apoptosis by destroying mitochondria. In addition, amantadine induces the initiation of autophagy and inhibits the fusion of autophagosome and lysosome, consequently performing an anti-glioma role. Taken together, our findings suggest that amantadine could be a promising anti-glioma drug that inhibits glioma cells by inducing apoptosis and autophagy, which may provide a novel potential treatment option for patients.
研究领域:
肿瘤学
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神经科学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2016
·Vol. 4
·期 23
·4110-4118
·
IF 4.872
Jing Zhang,Guangyu Hao,Chenfei Yao,Su Hu,Chunhong Hu,Bingbo Zhang
Glioma stem cells (GSCs) are considered the key to the occurrence, development, invasion, recurrence and sensitivity to treatment of brain tumors. Precise molecular imaging of GSCs by means of probes in vivo has therefore become a premise of solving the above problems. Herein, a sensitive, specific, accurate and biocompatible molecular nanoprobe is reported with MR/fluorescence imaging modalities for CD133+ glioma tumor bimodal targeted imaging. Cd-free high quality CuInS2/ZnS core/shell quantum dots (QDs) were synthesized for fluorescence imaging; DTPA-coupled BSA with Gd3+ chelation (BSA-DTPAGd) were prepared and used both for phase transfer of hydrophobic CuInS2/ZnS QDs and MR imaging modality. The resulting hydrophilic paramagnetic QDs (pQDs) were then linked with anti-CD133 monoclonal antibody, pQDs-CD133mAb denoting the framework of the entire molecular probe, for tumor targeting. The obtained pQDs-CD133mAb has a proper size (ca. 45 nm) and good colloidal stability. It exhibits a high quality fluorescent emission (ca. 630 nm) together with high longitudinal relaxivity (r1 = 15.2 mM−1 s−1) compared with that of commercial Magnevist (r1 = 3.12 mM−1 s−1). Dual modal imaging in vitro and in vivo shows potent tumor enhancement with administration of pQDs-CD133mAb. A biodistribution study indicates hepatobiliary and renal processing of pQDs-CD133mAb with no obvious toxicity. It could be therefore concluded, with a dual-modal imaging and targeting strategy, pQDs-CD133mAb presents a great potential as an alternative for accurate diagnosis of glioma.
研究领域:
医学影像学
·
肿瘤学
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Brain Sciences
·
2022
·Vol. 12
·期 9
·1138
·
IF 3.333
Ming-Chun Yang,Di Wu,Hui Sun,Lian-Kun Wang,Xiao-Feng Chen
Background: Glioma is one of the major health problems worldwide. Biomarkers for predicting the prognosis of Glioma are still needed. Methods: The transcriptome data and clinic information on Glioma were obtained from the CGGA, TCGA, GDC, and GEO databases. The immune infiltration status in the clusters was compared. The genes with differential expression were identified, and a prognostic model was developed. Several assays were used to detect RPH3A’s role in Glioma cells, including CCK-8, colony formation, wound healing, and transwell migration assay. Results: Lower Grade Glioma (LGG) was divided into two clusters. The immune infiltration difference was observed between the two clusters. We screened for genes that differed between the two groups. WGCNA was used to construct a co-expressed network using the DEGs, and four co-expressed modules were identified, which are blue, green, grey, and yellow modules. High-risk patients have a lower overall survival rate than low-risk patients. In addition, the risk score is associated with histological subtypes. Finally, the role of RPH3A was detected. The overexpression of RPH3A in LGG cells can significantly inhibit cell proliferation and migration and regulate EMT-regulated proteins. Conclusion: Our study developed a metabolic-related model for the prognosis of Glioma cells. RPH3A is a potential therapeutic target for Glioma.Keywords:glioma;metabolic signature;prognosis
研究领域:
肿瘤学
·
分子生物学
·
生物信息学
·
癌症生物学
✓ 已验证
产品关联
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
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神经科学
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药理学
✓ 已验证
DOI
PubMed
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