Frontiers in Chemistry
·
2025
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IF 4.2
Zhihong Hu,Xixi Hou,Yongjing Ren,Ziyuan Wu,Dong Yan,Hong Chen,Lan Wang
Cervical cancer ranks as the fourth most common cancer among women. However, the current treatments have significant side effects and limited therapeutic effects on advanced diseases, so it is necessary to discover better treatments for cervical cancer. The current study investigated the potential anticancer effects of a series of gefitinib-1,2,3-triazole derivative on Hela cells. Among the investigated, the target compound c13 showed good anticancer activity against Hela cells (IC50 = 5.66 ± 0.35 μM) compared with gefitinib (IC50 = 14.18 ± 3.19 μM). Moreover, compound c13 significantly inhibited the colony formation ability of Hela cells in a dose-dependent manner, accompanied by morphological changes in HeLa cells. Further investigations demonstrated that compound c13 triggered cell apoptosis and arrested the cell cycle at the G2/M phase in Hela cells. In addition, western blot analysis revealed that compound c13 upregulated the Bax/Bcl-2 ratio, and increased the levels of active caspase 3 and PARP1 cleavage, which suggested the involvement of the mitochondrial pathway in compound c13-induced apoptosis. In brief, these results indicated that compound c13 is a promising compound for the treatment of cervical cancer.
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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产品关联
DOI
PubMed
高影响因子
ANNALS OF THE RHEUMATIC DISEASES
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2024
·
IF 20.3
Fang Qiu,Duoli Xie,Hongzhen Chen,Zhuqian Wang,Jie Huang,Chunhao Cao,Yiying Liang,Xu Yang,Dong-Yi He,Xuekun Fu,Aiping Lu,Chao Liang
Objectives Rheumatoid arthritis (RA) is an autoimmune disease characterised by aggressive fibroblast-like synoviocytes (FLSs). Very few RA patients-derived FLSs (RA-FLSs)-specific surface signatures have been identified, and there is currently no approved targeted therapy for RA-FLSs. This study aimed to screen therapeutic aptamers with cell-targeting and cytotoxic properties against RA-FLSs and to uncover the molecular targets and mechanism of action of the screened aptamers. Methods We developed a cell-specific and cytotoxic systematic evolution of ligands by exponential enrichment (CSCT-SELEX) method to screen the therapeutic aptamers without prior knowledge of the surface signatures of RA-FLSs. The molecular targets and mechanisms of action of the screened aptamers were determined by pull-down assays and RNA sequencing. The therapeutic efficacy of the screened aptamers was examined in arthritic mouse models. Results We obtained an aptamer SAPT8 that selectively recognised and killed RA-FLSs. The molecular target of SAPT8 was nucleolin (NCL), a shuttling protein overexpressed on the surface and involved in the tumor-like transformation of RA-FLSs. Mechanistically, SAPT8 interacted with the surface NCL and was internalised to achieve lysosomal degradation of NCL, leading to the upregulation of proapoptotic p53 and downregulation of antiapoptotic B-cell lymphoma 2 (Bcl-2) in RA-FLSs. When administrated systemically to arthritic mice, SAPT8 accumulated in the inflamed FLSs of joints. SAPT8 monotherapy or its combination with tumour necrosis factor (TNF)-targeted biologics was shown to relieve arthritis in mouse models. Conclusions CSCT-SELEX could be a promising strategy for developing cell-targeting and cytotoxic aptamers. SAPT8 aptamer selectively ablates RA-FLSs via modulating NCL-p53/Bcl-2 signalling, representing a potential alternative or complementary therapy for RA.
研究领域:
免疫学
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分子生物学
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治疗学
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自身免疫疾病
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产品关联
DOI
PubMed
高影响因子
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
·
2024
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IF 3.9
Ying Sun,Xiaohui Jin,Zuwang Yang,Zunhan Hu,Qiulu Li,Jingquan Dong,Mian Fu
Difenoconazole (DFZ) is a widely used triazole fungicide in agricultural production. However, the presence of DFZ residue in the environment poses a significant risk to non-target organisms. Ferulic acid (FA) is a phenolic compound known for its antioxidant and anti-inflammatory properties. This study aims to investigate the hepatic damage caused by DFZ in carp and explore the mechanism through which FA alleviates this damage. The findings revealed that FA enhanced the antioxidant capability of the carp's liver and reduced the accumulation of reactive oxygen species (ROS) in the liver tissue. Moreover, FA regulated the transcriptional levels of inflammation-related factors, effectively preventing the inflammatory response triggered by the NF-κB signaling pathway. Additionally, TUNEL results demonstrated that DFZ initiated apoptosis, while dietary supplementation with FA decreased the protein expression levels of Bax and Cytochrome C (Cyt c) and the transcriptional levels of bax , caspase3 , caspase9 , p53 genes. Furthermore, FA increased the protein expression and transcriptional levels of Bcl-2. In conclusion, FA protects against liver injury induced by DFZ exposure in carp by modulating oxidative damage, inflammation, and apoptosis.
研究领域:
环境毒理学
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水生生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
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2022
·Vol. 30
·期 1
·1060-1071
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IF 5.19
Zhang Xinyu,Sun Kexin,Wang Xu,Shi Xu,Gong Duqiang
Chlorpyrifos (CPF), an organophosphorus pesticide, is detected commonly in environments, where it is thought to be highly toxic to non-target organisms. However, the mechanism of CYP450s pathway mediated by nuclear receptors on CPF-induced apoptosis and necroptosis at the cellular level and the effect of CPF on the cytotoxicity of the chicken hepatocarcinoma cell line (LMH) has also not been reported in detail. Therefore, this experiment aims to explore whether CPF can improve apoptosis and necroptosis in LMH cells by activating the nuclear receptors/CYP450s axis. LMH cells, the subject of this study, were exposed to 5 μg/mL, 10 μg/mL, and 15 μg/mL doses of CPF. With the increase of CPF concentration, the increase of nuclear receptor level led to the up-regulation of CYP450s activity. With the massive production of ROS, the expression of apoptotic pathway genes (Bax, Caspase9, and Caspase3) enhanced, while Bcl-2 expression dropped sharply. The expression of programmed necroptosis genes (RIPK1, RIPK3, and MLKL) heightened, and Caspase8 reduced considerably. In short, our data suggests that excessive activation of nuclear receptors and CYP450s induced by CPF promotes ROS production, which directs apoptosis and programmed necroptosis in LMH cells. Graphical abstract
研究领域:
毒理学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
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2022
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IF 4.601
Guizhen Liu,Yanan Du,Tao Fu,Ying Han,Lifeng Pan,Jingwu Kang
An approach for profiling protein-protein interactions by using affinity purification with capillary monolithic immobilized metal affinity chromatography column (cm-IMAC) in combination with label free quantitative proteomics was described in the present work. The cm-IMAC columns were prepared in a single step by copolymerization of the function monomer , namely ( S )-2,2′-((1-carboxy-5-(pent‑4-enamido)pentyl)azanediyl)diacetic acid which provide a nitrilotriacetate (NTA) moiety to form chelated complexation with Ni (II) ions, inside the fused silica capillaries. The His 6 -tagged bait protein can be easily immobilized on the cm-IMAC columns through the formation of chelating complexation with the NTA-Ni (II) functional groups of the matrix. The cm-IMAC columns were used to explore protein-protein interactions (PPIs) on a proteomic scale when combined with label-free proteomics. A known interaction pair of proteins, namely NDP52 (amino acid sequence 10–126) and NAP1 (33–75) as well as Bcl-2 family proteins were used for proof of concept. New interactors of Bcl-X L were identified and validated by co-immunoprecipitation.
研究领域:
生物化学
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蛋白质组学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2024
·Vol. 25
·期 21
·11686
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IF 4.9
Kangli Wang,Lingchen Tao,Meifei Zhu,Xinyu Yu,Yuanyuan Lu,Bin Yuan,Fuliang Hu
Melittin has previously been found to have a positive effect on colorectal cancer (CRC) treatment, one of the most difficult-to-treat malignancies, but the mechanism by which this effect occurs remains unclear. We evaluated melittin’s pro-apoptotic and anti-metastatic effects on CRC in vitro and in vivo. The results showed that melittin-induced mitochondrial ROS bursts decreased ΔΨm, inhibited Bcl-2 expression, and increased Bax expression in both cells and tumor tissues. This led to increased mitochondrial membrane permeability and the release of pro-apoptotic factors, particularly the high expression of Cytochrome C, initiating the apoptosis program. Additionally, through wound-healing and transwell assays, melittin inhibited the migration and invasion of CRC cells. In vivo, the anti-metastatic effect of melittin was also verified in a lung metastasis mouse model. Western blotting and immunohistochemistry analysis indicated that melittin suppressed the expression of MMPs and regulated the expression of crucial EMT markers and related transcription factors, thereby inhibiting EMT. Furthermore, the melittin disrupts neovascularization, ultimately inhibiting the metastasis of CRC. In conclusion, melittin exerts anti-CRC effects by promoting apoptosis and inhibiting metastasis, providing a theoretical basis for further research on melittin as a targeted therapeutic agent for CRC.
研究领域:
肿瘤学
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分子生物学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
PLoS One
·
2025
·Vol. 20
·期 7
·e0328000
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IF 2.6
Shuaijun Peng,Ruiqin Sun,Hui Liu,Baoying Wang,Yucheng Li
Gastric mucosal injury can lead to significant gastrointestinal disorders, including inflammation, ulcers, and intestinal metaplasia in severe cases. Although bile acids are known contributors to mucosal damage due to their acidity, the role of chenodeoxycholic acid (CDCA), a primary bile acid, in gastric mucosal injury remains unclear. This study investigates the role of CDCA in inducing gastric mucosal injury and its underlying mechanisms, with a focus on apoptosis and FXR activation, to identify potential therapeutic targets. Mice were administered varying doses of CDCA to evaluate changes in body weight, food intake, and gastric mucosal pathology using hematoxylin-eosin (HE) and alcian blue-periodic acid-Schiff (AB-PAS) staining. Expression levels of apoptosis-related genes (BAX, BCL-2) and the intestinal metaplasia marker gene (CDX2) were analyzed via RT-PCR and Western blotting (WB). GES-1 cells were treated with different CDCA concentrations to assess cell viability via the CCK-8 assay. Apoptosis rates were measured using flow cytometry, and FXR inhibitors were applied to examine their impact on CDCA-induced effects. CDCA administration in mice resulted in weight loss, reduced food and water intake, gastric epithelial shedding, and intestinal metaplasia. CDCA exposure upregulated Bax and CDX2 expression, while reducing BCL-2 levels. In vitro, CDCA inhibited GES-1 cell viability and increased apoptosis rates, effects that were reversed by FXR inhibition. CDCA induces gastric mucosal injury through apoptosis and FXR activation. These findings provide insights into the mechanisms of bile acid-mediated mucosal damage and highlight FXR as a potential therapeutic target for gastric mucosal disorders.
研究领域:
胃肠病学
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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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病理学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2021
·
IF 6.53
Wei-ni Qin,Kai-cheng Zhang,Ting Geng,Fang-fang Cheng,Pei-dong Chen,Wei-feng Yao,Li Zhang,Yu-dan Cao
Euphorbiae pekinensis Radix (EP) is effective in treating various diseases, but it’s toxicity is a major obstacle in use in clinical. Although EP was processed with vinegar to reduce it’s toxicity, the detailed mechanism of toxicity in EP have not been clearly delineated. This study investigate the toxicity attenuation-mechanism of Euphorbiae pekinensis after being processed with vinegar (VEP) and the toxic mechanism of four compounds from EP on zebrafish embryos. The contents of four compounds decreased obviously in VEP. Correspondingly, slower development on embryos can be seen as some symptoms like reduction of heart rate, liver area and gastrointestinal peristalsis after exposed to the compounds. Some obvious pathological signals such as pericardial edema and yolk sac edema were observed. Furthermore, the compounds could increase the contents of MDA and GSH-PX and induce oxidative damage by inhibiting the activity of SOD. Also, four compounds could provoke apoptosis by up-regulating the expression level of p53, MDM2, Bax, Bcl-2 and activating the activity of caspase-3, caspase-9. In conclusion, the four compounds play an important role in the toxicity attenuation effects of VEP, which may be related to the apoptosis induction and oxidative damage. This would contribute to the clinical application and further toxicity-reduction mechanism research.
研究领域:
药理学
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毒理学
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发育生物学
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生物化学
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DOI
PubMed
高影响因子
JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2021
·Vol. 74
·期 4
·596-604
·
IF 3.765
Sun Liyun,Shang Huoli,Wu Yuzhen,Xin Xiujuan
ObjectivesThe combination of gemcitabine (Gem) and hypericin (HY) enhances the apoptosis of Capan-2 cells, providing a promising option for the treatment of pancreatic cancer. Our study further explored the cytotoxic mechanism of HY combined with chemotherapy drugs on pancreatic cancer.MethodsThe proliferation rate of the cells assayed with the MTT method. The ROS (reactive oxygen species) levels of each treatment were evaluated by DCFH-DA oxidisation methods. The activity of glutathione reductase and the levels of reduced glutathione (GSH) and oxidised glutathione (GSSG) were assessed using assay kits. The expression levels of apoptosis-related proteins were analysed by western blotting.Key findingsThe activity of glucose-6-phosphate dehydrogenase (G6PDH), a key enzyme of the pentose phosphate pathway, significantly decreased in Gem + HY groups, however, the ROS level enhanced accompanying with GSH depleting, mitochondrial membrane depolarisation and cytochrome C release. Gem + HY inhibits the expression of Bcl-2 but stimulates Bax level, triggering caspase activation and PARP cleavage and thus promoted apoptosis of Capan-2 cells.ConclusionsWe demonstrated that Gem combined HY-PDT could inhibit the proliferation of Capan-2 cells and induce cell apoptosis. HY-PDT combined with Gem had a great potential on pancreatic cancer treatment clinically.
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
DOI
PubMed
高影响因子
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
·
2020
·Vol. 47
·期 6
·1083-1091
·
IF 2.456
Zhu Wang,Qianqian Wang,Tao He,Wen Li,Yan Liu,Yuan Fan,Yanping Wang,Qi Wang,Jie Chen
Carboplatin (CBP) is a widely used targeted anticancer therapeutic drug; however, multi-drug resistance induced by the accumulation of CBP eventually causes diseases progression. The anti-malarial drug artesunate (ART) also exerts anticancer effects in various cancers; however, the combined effect of ART and CBP on non-small cell lung cancer (NSCLC) remains unclear. In the present study, the NSCLC cell line A549 was pretreated with various concentrations of CBP, ART and gemcitabine (GEM). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were conducted to detect cell viability. Cell apoptosis was evaluated by both flow cytometry and TUNEL apoptotic assay. The expression profiles of cell cycle-related proteins and apoptotic proteins were determined by western blot. Cell clone numbers were visualized using crystal violet staining. Here, we found that both CBP and ART suppressed cell viability, and promoted cell apoptosis, and the combined application of ART and CBP at a lower concentration exhibited synergistic effects. Specifically, the combination of ART and CBP at a lower concentration suppressed cell clone numbers, promoted cell cycle arrest at the G 2 /M phase, and induced the expression of the cell cycle and apoptosis-related proteins BAX, p21, p53, and Caspase-3, while decreasing Bcl-2 and Cyclin B1 expression. Based on these results, we concluded that combined application of ART and CBP exerts synergistic anti-tumour effects on NSCLC by enhancing cell apoptosis in a mitochondria-dependent manner.
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
ENVIRONMENTAL POLLUTION
·
2019
·
IF 5.714
Da Lv,Yi Gu,Ming Guo,Ping Hou,Yan Li,Ronghui Wu
To better understand the toxicological activities of perfluorooctanoic acid (PFOA), we examined the effects of PFOA on apoptosis and its molecular mechanism in SMMC-7721 hepatoma cells. Cell viability was evaluated by MTT assay and apoptosis was determined by flow cytometry. Western blot and quantitative real-time PCR were used to examine the protein and gene expressions of Bax and Bcl-2. Our results showed that PFOA inhibited SMMC-7721 cell growth and induced apoptosis. PFOA treatment increased Bax expression and increased Bcl-2 expression at both gene and protein levels. Our study demonstrated that PFOA had toxic effects on SMMC-7721 cells, such as inhibiting cell proliferation and inducing apoptosis. Furthermore, we showed that PFOA-mediated induction of apoptosis involved inducing Bax and decreasing Bcl-2 expression as a molecular mechanism of its toxicological effects.
研究领域:
毒理学
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细胞生物学
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癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2022
·
IF 7.419
Huixiao Yuan,Xin Huang,Qingqing Li,Cici Luo,Chenyu Lin,Shuxian Zhang,Yaguang Zhang,Zhilin Yan,Ning Du,Zhongmin Liu,Hua Jiang,Bingdi Chen
Novel functions and involvement of circFARSA have not been reported in pancreatic cancer; in addition, its inhibitor screening has not yet been conducted. The purpose of this study was to (1) verify circFARSA as a novel anti-cancer target for pancreatic cancer and (2) to prepare a novel anti-pancreatic cancer agent targeting circFARSA. In this study, we designed and synthesized a small interfering RNA (siRNA, named siRNA-circFARSA), which specifically inhibits circFARSA expression. Using liposomes and porous silicon nanoparticles (pSiNPs) as siRNA delivery system, we prepared liposome-siRNA-circFARSA and pSiNP-PEI-siRNA-circFARSA and investigated their anti-cancer mechanism by quantitative real-time PCR and western blotting. Cell proliferation curves and transwell migration assays were performed to investigate the effect of siRNAs proliferation and migration capabilities of cancer cells. Patient-derived tumor xenograft mouse models were used to investigate the anti-cancer effects in vivo . The data showed that both liposome-siRNA-circFARSA and pSiNP-PEI-siRNA-circFARSA (Si: 0.7 µg/mL) significantly inhibited the proliferation and migration of pancreatic cancer cells in vitro . However, the biological safety and in vivo anti-cancer effects of pSiNP-PEI-siRNA-circFARSA (Si: 22.4 µg/mL) were higher than those of liposome-siRNA-circFARSA. The results showed that siRNA-circFARSA could inhibit the expression of circFARSA and then BCL-2 protein expression, thereby leading to pancreatic cancer cell apoptosis after transportation into pancreatic cancer cells. Therefore, this study provides tools for pancreatic cancer treatment in the future, as it (1) verified circFARSA as a novel target for pancreatic cancer treatment, and (2) prepared a novel anti-pancreatic cancer agent (pSiNP-PEI-siRNA-circFARSA).
研究领域:
肿瘤学
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分子生物学
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纳米技术
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药学
✓ 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）