Nanoscale Research Letters
·
2011
·Vol. 6
·期 1
·1-10
·
IF 2.56
Kai Wei,Xiaojun Xu,Ximing Pu,Zhenqing Hou,Qiqing Zhang
The evaluation of the toxicity of magnetic nanoparticles (MNPs) has attracted much attention in recent years. The current study aimed to investigate the cytotoxic effects of Fe 3 O 4 , oleic acid-coated Fe 3 O 4 (OA-Fe 3 O 4 ), and carbon-coated Fe (C-Fe) nanoparticles on human hepatoma BEL-7402 cells and the mechanisms. WST-1 assay demonstrated that the cytotoxicity of three types of MNPs was in a dose-dependent manner. G1 (Fe 3 O 4 and OA-Fe 3 O 4 ) phase and G2 (C-Fe) phase cell arrests and apoptosis induced by MNPs were detected by flow cytometry analysis. The increase in apoptosis was accompanied with the Bax over-expression, mitochondrial membrane potential decrease, and the release of cytochrome C from mitochondria into cytosol. Moreover, apoptosis was further confirmed by morphological and biochemical hallmarks, such as swollen mitochondria with lysing cristae and caspase-3 activation. Our results revealed that certain concentrations of the three types of MNPs affect BEL-7402 cells viability via cell arrest and inducing apoptosis, and the MNPs-induced apoptosis is mediated through the mitochondrial-dependent pathway. The influence potency of MNPs observed in all experiments would be: C-Fe > Fe 3 O 4 > OA-Fe 3 O 4 .
研究领域:
纳米技术
·
毒理学
·
细胞生物学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MEDICAL SCIENCE MONITOR
·
2018
·
IF 1.894
Youxia Huang,Yingjian Cai,Ronggui Huang,Xingzhong Zheng
Background Hepatic carcinoma is the third leading cause of cancer-related deaths. This study aimed to evaluate the anti-tumor effects of rosmarinic acid (RosA) combined with Adriamycin (ADM) on proliferation and apoptosis of hepatic carcinoma cell lines. Material/Methods Human HepG2 and Bel-7402 cells were treated with RosA and ADM and divided into HepG2 or Bel-7402, 25 μg/ml, 50 μg/m, and 100 μg/ml RosA+0.4 μg/ml ADM groups, respectively. The Cell Counting Kit-8 (CCK-8) assay was used to evaluate cell viability. Immunohistochemistry assay was used to examine B cell lymphoma-2 (Bcl-2) and Bcl-2-associated X (Bax) expression. Cell cycle analysis was used to detect cell cycle distribution. Flow cytometry and terminal deoxynucleotidyl transferase-mediated d-UTP nick-end labeling (TUNEL) assay were utilized to evaluate apoptosis. Results RosA combined with ADM damaged cell morphology and decreased cell viability, and significantly decreased S-phase cell numbers compared to the HepG2 or Bel-7402 group ( p <0.05). Apoptosis rates in the RosA combined with ADM group were significantly increased compared to the HepG2 or Bel-7402 group ( p <0.05). TUNEL assay showed that RosA combined with ADM significantly induced DNA damage (TUNEL-positive staining) in the HepG2 and Bel-7402 groups ( p <0.05). RosA combined with ADM significantly reduced Bcl-2 expression in HepG2 or Bel-7402 cells ( p <0.05). RosA combined with ADM significantly increased Bax expression in HepG2 and Bel-7402 cells ( p <0.05). Cell viability, apoptosis, cell cycle, and Bcl-2 and Bax expression were changed with increased concentrations of RosA. Conclusions RosA combined with ADM damaged tumor cell morphologies, decreased cell viability, and induced apoptosis of HepG2 and Bel-7402 by triggering the mitochondria-mediated signaling pathway.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULES
·
2025
·Vol. 30
·期 8
·1667
·
IF 4.6
Zenan Chen,Wei Li,Yan Zhao,Dingrui Liu,Jiahong Han,Enbo Cai
Tumorigenesis and progression are closely associated with apoptosis and primarily regulated by mitochondria, which are considered major targets for cancer therapy. In this study, twelve novel icaritin (ICT) derivatives were designed and synthesized, four of which were specifically targeted to mitochondria. Biological studies demonstrated that all compounds containing triphenylphosphine (TPP+) exhibited a substantial increase in antitumor activity compared to ICT and control compounds while also exhibiting notable selectivity for tumor cells over normal cells. Among these derivatives, Mito-ICT-4 exhibited the strongest antiproliferative effect, with an IC50value of 0.73 ± 0.06 μM for BEL-7402 cells, which is 29 times lower than that of ICT, and an IC50value of 67.11 ± 2.09 μM for HEK293 cells, indicating approximately 33-fold selectivity for tumor cells. High-performance liquid chromatography (HPLC) analysis revealed that Mito-ICT-4 significantly accumulated in the mitochondria of BEL-7402 cells, with the level of accumulation approximately 2.5 times greater than that of ICT. Further investigations demonstrated that upon entering the mitochondria of tumor cells, Mito-ICT-4 downregulated SIRT3 protein expression, disrupted intracellular redox homeostasis, and led to a substantial increase in mitochondrial ROS levels, abnormal CypD-dependent MPTP opening, mitochondrial membrane potential depolarization, and ROS release into the cytoplasm, ultimately triggering ROS-mediated apoptosis in BEL-7402 cells. Transcriptomic analysis identified differentially expressed genes and enriched pathways, highlighting the ROS-mediated p38-MAPK signaling pathway as a key mediator of Mito-ICT-4-induced mitochondria-dependent apoptosis. The effects of Mito-ICT-4 on the expression of key genes (SIRT3, CypD, P-MKK6, P-P38, and DDIT3) were further validated by qRT-PCR and Western blot analysis, with results aligning with transcriptomic data. The novel ICT derivatives synthesized in this study, with mitochondria-targeting functionality, provide a basis for the development of targeted antitumor drugs.
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
Stem Cell Research & Therapy
·
2024
·Vol. 15
·期 1
·1-15
·
IF 7.1
Wang Ping,Wang Min,Liu Lin,Li Hongyi,Liu Helin,Ren Jiangbo,Liu Tianhui,Cong Min,Zhu Zhijun,Zhao Xinyan,Sun Liying,Jia Jidong
Background Hepatic progenitor cells serve not only as the origin of combined hepatocellular cholangiocarcinoma (cHCC-CCA) but are also responsible for malignancy recurrence after surgical resection. Nucleophosmin 1 (NPM1) has been implicated in cancer metastasis and poor prognosis. This study aimed to determine the expression of NPM1 by hepatic progenitor cells in cHCC-CCA and the effects of targeting NPM1 on hepatic progenitor cells and BEL-7402 cells with characteristics of both progenitor cells and cHCC-CCA. Methods First, NPM1 was detected by RT‒PCR, western blotting, and double-immunofluorescence staining in cHCC-CCA tissues. NPM1 expression was subsequently analysed in rat hepatic progenitor cells cultured in vitro and in interleukin 6 (IL6)-treated cells. The effects and mechanism of NPM1 on hepatic progenitor cells were determined by knocking down NPM1 and performing RNA sequencing analysis. Finally, NSC348884, a small-molecule inhibitor that disrupts NPM1 dimer formation, was used to confirm the function of NPM1 in BEL-7402 cells. Results Both human hepatic progenitor cells in cHCC-CCA tissues and rat in vitro cultured hepatic progenitor cells highly expressed NPM1. IL6, a cytokine involved in the malignant transformation of hepatic progenitor cells, dose-dependently increased NPM1 and PCNA expression. Knocking down NPM1 reduced IL6R transcription ( P < 0.0001) and inhibited the proliferation ( P = 0.0065) of hepatic progenitor cells by suppressing the mTOR signalling pathway and activating the apoptosis pathway. Furthermore, knocking down NPM1 in hepatic progenitor cells resulted in more apoptotic cells (7.33 ± 0.09% vs. 3.76 ± 0.13%, P < 0.0001) but fewer apoptotic cells in the presence of NSC348884 (47.57 ± 0.49% vs. 63.40 ± 0.05%, P = 0.0008) than in the control cells, suggesting that low-NPM1-expressing cells are more resistant to NSC348884. In addition, NSC348884 induced the apoptosis of BEL-7402 cells with an IC50 of 2.77 μmol/L via the downregulation of the IL-6R and mTOR signalling pathways and inhibited the growth of BEL-7402 cells in a subcutaneous xenograft tumour model ( P = 0.0457). Conclusions Targeting NPM1 inhibits proliferation and induces apoptosis in hepatic progenitor cells and BEL-7402 cells, thus serving as a potential therapy for cHCC-CCA.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2020
·
IF 5.977
Tingting Niu,Guoxing Yin,Ting Yu,Yabing Gan,Chenye Zhang,Juanjuan Chen,Wei Wu,Haimin Chen,Haitao Li,Peng Yin
Monitoring cellular GSH dynamics is of great value to understand its complex biological functions and related diseases. It still remains challenging to understand the mechanism of GSH dynamics in complex intracellular environment. Herein, a novel fluorescent probe featured with chlorinated coumarin-TCF was exploited for sensing of GSH with high selectivity and high sensitivity. Large fluorescence enhancement at 471 nm was observed upon addition of GSH with large emission distance ( Δλ em = 219 nm). This novel probe was successfully applied to monitor endogenous and exogenous GSH dynamics without interference of other thiols via fluorescence imaging. More importantly, using this probe, low dose reactive oxygen species induced GSH increasement through nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signal pathway in BEL-7402 cells was observed. This novel fluorescent probe has the potential for quantitative monitoring of cellular GSH, which will promote further understanding of its physiological and pathological roles in biological systems.
研究领域:
生物化学
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULES
·
2018
·Vol. 23
·期 9
·2187
·
IF 3.098
Hui Wang,Wenxi Zhang,Yatao Cheng,Xinyu Zhang,Nannan Xue,Gaorong Wu,Meng Chen,Kang Fang,Wenbo Guo,Fei Zhou,Herong Cui,Tao Ma,Penglong Wang,Haimin Lei
In the clinic some anti-tumor drugs have shown damage to normal blood vessels, which could lead to vascular diseases. Therefore, it is necessary to evaluate the effects of anti-tumor drugs on normal blood vessels at the beginning of the drug design process. In this study, ligustrazine (TMP) and flavonoids were selected as raw materials. Sixteen novel TMP-flavonoid derivatives were designed and synthesized. Interestingly, compounds14and16were obtained by hydrolysis of a dihydroflavone to a chalcone under alkaline conditions. The cytotoxicity of the TMP-flavonoid derivatives was evaluated on five human tumor cell lines and one classical type of normal endothelial cell lines (HUVEC-12) by an MTT assay. Part of the derivatives showed better anti-tumor activities than the corresponding raw materials. Among them, compound14exhibited the closest activity to the positive control against the Bel-7402 cell line (IC50= 10.74 ± 1.12 μM; DDP IC50= 6.73 ± 0.37 μM) and had no toxicity on HUVEC-12 (IC50> 40 μM). Subsequently, fluorescence staining and flow cytometry analysis indicated that compound14could induce apoptosis of Bel-7402 cell lines. Moreover, the structure-activity relationships of these derivatives were briefly discussed.Keywords:TMP-flavonoid derivatives;anti-tumor;human tumor cell lines;HUVEC-12;fluorescence staining;flow cytometry
研究领域:
药理学
·
肿瘤学
·
药物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF HETEROCYCLIC CHEMISTRY
·
2014
·Vol. 52
·期 2
·473-477
·
IF 0.873
Hongxia Liu,Libo Li,Shaikh Qurat-ul-ain,Tao Jiang
A series of novel 2,6-disubstituted purine derivatives were designed and synthesized from 2,6-dichloropurine. The structures of target compounds were determined by 1 H-NMR, 13 C-NMR, and HRMS. The synthesized compounds were evaluated for their inhibitory activities against lung cancer cell lines of A549 and liver cancer cell lines of Bel-7402. 2-(4-Benzyloxy-phenylamino)-6-(cyclohexylamino)purine( 3 ), 2-(4-chloro-phenylamino)-6-( n -butylamino)purine ( 5 ), 2-(4-morpholinoamino)-6-(4-hydroxy-phenylamino)purine ( 9 ), and 2-(4- O -galactosyl-phenylamino)-6-(cyclohexylamino)purine ( 12 ) exhibited moderate inhibitory activity.
研究领域:
药物化学
·
肿瘤学
·
有机合成
✓ 已验证
DOI
高影响因子
PLANTA MEDICA
·
2022
·Vol. 88
·期 13
·1233-1244
·
IF 3.007
Shipeng Chen,Yinan Liao,Jinyan Lv,Huaxin Hou,Jie Feng
The aim of the present study was to investigate the cytotoxic effects and underlying molecular mechanisms of nitidine chloride (NC) in hepatocellular carcinoma cells via quantitative proteomics. MTT assays were used to detect the inhibitory effects of NC in Bel-7402 liver cancer cells, and the number of apoptotic cells was measured by flow cytometry. Quantitative proteomics technology based on iTRAQ was used to discover differential expressed proteins after NC treatment, and bioinformatic techniques were further used to screen potential targets of NC. Molecular docking was applied to evaluate the docking activity of NC with possible upstream proteins, and their expression was detected at the mRNA and protein levels by quantitative reverse transcription PCR and western blotting. NC inhibited the proliferation of Bel-7402 cells after 24 h of treatment and stimulated apoptosis in vitro. The proteomics experiment showed that NC triggers mitochondrial damage in HCC cells and transcription factor AP-1 (c-Jun) may be a potential target of NC (fold change = 4.36 ± 0.23). Molecular docking results revealed the highest docking score of NC with c-Jun N-terminal kinase (JNK), one of the upstream proteins of c-Jun. Moreover, the mRNA and protein expression of c-Jun and JNK were significantly increased after NC treatment (p
研究领域:
癌症生物学
·
分子生物学
·
药理学
·
蛋白质组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DYES AND PIGMENTS
·
2018
·
IF 3.767
Longbin Xu,Xu He,Pinyi Ma,Xin Liu,Fangmei Zhang,Ying Sun,Daqian Song,Xinghua Wang
Alkaline phosphatase (ALP) is an essential enzyme in various tissues, which has been reported to be extensively involved in various physiological and pathological processes. Fluorescent probe assays carried out in vivo are desirable for monitoring the ALP activity. In this study, a novel red-light fluorescent DHP probe, which exhibited good selectivity and high sensitivity, for monitoring the ALP activity in real time was described. The DHP probe exhibited good water solubility, and the detection limit of ALP was determined as 0.031 U/L; this value is almost less than those of the other probes reported previously. The probe exhibited high selectivity, which will not interfere with various enzymes and amino acids. Moreover, the sensing and luminescence mechanisms of ALP to DHP was investigated by density functional theory (DFT) and time-dependent DFT. Furthermore, the DHP probe was applied for the detection of endogenous ALP in BEL-7402 cells, and the fluctuation of the ALP levels in BEL-7402 and HEK 293 T cells was successfully tracked by fluorescence microscopy .
研究领域:
生物化学
·
细胞生物学
·
分子生物学
·
分析化学
✓ 已验证
产品关联
DOI
高影响因子
ANALYST
·
2012
·Vol. 137
·期 6
·1389-1395
·
IF 4.23
Huanshun Yin,Yunlei Zhou,Chuanxia Chen,Lusheng Zhu,Shiyun Ai
The abnormal expression of microRNAs (miRNAs) in many solid tumors makes miRNAs potential biomarkers for disease diagnosis and highlights the need for the sensitive and selective detection of miRNAs. In the present work, an ‘off-on’ signaling genosensor platform for miRNA-21 detection was well developed. This tactic was based on a locked nucleic acid-integrated nucleic acid hairpin probe, a biotin-labeled bridge DNA–AuNPs–bio-barcode signal amplification unit and enzymatic signal amplification. The test is simple, fast and ultrasensitive with a linear range of 0.01–700 pM. The detection limit was estimated to be 6 fM. The overexpression of miRNA-21 was confirmed in total RNA extracted from human hepatocarcinoma cells BEL-7402 and human HeLa cells compared with the control sample extracted from normal human hepatic L02 cells. This method does not need miRNA-21 labeling, isolation, enrichment or PCR amplification. The performance of the assay developed here could satisfy the need for rapid, easy, sensitive and specific early cancer diagnosis in clinical diagnostics.
研究领域:
生物化学
·
分子生物学
·
癌症研究
·
生物技术
✓ 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）