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JOURNAL OF FOOD SCIENCE · 2024 · IF 3.2

Chondroitin sulfate–functionalized selenium nanoparticle–induced S-phase cell cycle arrest and apoptosis in HeLa Cells

Jianping Chen,Xuehua Chen,Anqi Tang,Zhuo Wang,Kit-Leong Cheong,Xiaofei Liu,Saiyi Zhong

This study aimed to evaluate the anti-cervical cancer activity of chondroitin sulfate–functionalized selenium nanoparticles (SeCS) and to elucidate their action mechanism. Cytotoxic effect of SeCS on HeLa cells was assessed by MTT assay. Further molecular mechanism of SeCS was analyzed by flow cytometric assay and western blotting. The results showed that treatment with SeCS resulted in a dose- and time-dependent inhibition in the proliferation of HeLa cells. The data obtained from flow cytometry demonstrated that SeCS inhibited HeLa cell growth via the induction of S-phase arrest and cell apoptosis. Further mechanism analysis found that SeCS down-regulated expression levels of cyclin A and CDK2 and up-regulated p21 expression, which contributed to S arrest. Moreover, SeCS increased the level of Bax and decreased the expression of Bcl-2, resulting in the release of cytochrome C from mitochondria and activating caspase-3/8/9 for caspase-dependent apoptosis. Meanwhile, intracellular reactive oxygen species (ROS) levels were elevated after SeCS treatment, suggesting that ROS might be upstream of SeCS-induced S-phase arrest and cell apoptosis. These data show that SeCS has anti-tumor effects and possesses the potential to become a new therapeutic agent or adjuvant therapy for cancer patients. Practical Application In our previous study, we used chondroitin sulfate to stabilize nano-selenium to obtain SeCS to improve the bioactivity and stability of nano-selenium. We found that it possessed an inhibitory effect on HeLa cells. However, the molecular mechanism remains unclear. This study elucidated the mechanism of SeCS damage to HeLa cells. SeCS has the potential to become a new therapeutic agent or adjuvant therapy for cancer patients.

研究领域: 肿瘤学 · 纳米技术 · 细胞生物学 · 药学
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RSC Advances · 2017 ·Vol. 7 ·期 43 ·26625-26632 · IF 3.108

Microwave-assisted synthesis of polypyridyl ruthenium(II) complexes as potential tumor-targeting inhibitors against the migration and invasion of Hela cells through G2/M phase arrest

Jieqiong Cao,Qiong Wu,Wenjie Zheng,Li Li,Wenjie Mei

A series of polypyridyl ruthenium(II) complexes coordinated by phenanthroimidazole derivatives [Ru(phen)2(R)](ClO4)2 (where 1 R = IP, 2 R = PIP, 3 R = p-HPIP, 4 R = p-OCH3PIP) was synthesized with an average yield of >85% under microwave irradiation at 140 °C for 30 min. The inhibitory effect of these complexes against various tumour cells were evaluated by MTT assay, and the results showed that these polypyridyl ruthenium(II) complexes exhibited acceptable inhibition against different tumour cells, especially 4, with an IC50 of 18.4 μM for Hela cells. The results showed that 4 inhibited the growth of cervical cancer Hela cells by inducing G2/M phase arrest, which was followed by slight apoptosis. Further studies showed that 4 displayed better inhibition against the invasion and metastasis of Hela cells than NAMI-A. Studies on the in vivo distribution and metabolism indicated that 4 was rapidly distributed in the entire body, absorbed by the tumour tissue and had only a small accumulation of toxicity in the body. These results demonstrated that this type of ruthenium(II) complex can block the growth of Hela cells and inhibit their migration and invasion through G2/M phase arrest, which suggests the complex could act as a potential tumour-targeting inhibitor in future clinical applications.

研究领域: 药理学 · 肿瘤学 · 生物化学
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MICROCHIMICA ACTA · 2019 ·Vol. 186 ·期 6 ·1-8 · IF 5.479

Electrochemical detection of superoxide anions in HeLa cells by using two enzyme-free sensors prepared from ZIF-8-derived carbon nanomaterials

Li Yufei,Zhang Huanhuan,Cai Xuan,Zhao Hongli,Magdassi Shlomo,Lan Minbo

Two kinds of carbon-based nanozymes were constructed from the same precursor of zeolitic imidazolate framework-8 (ZIF-8) for O 2 •− determination. Hollow carbon cubic nanomaterial (labelled as HCC) was obtained by chemically etching ZIF-8 with tannic acid and a subsequent calcination. A porous carbon cubic nanomaterial (labelled as PCC) was prepared by directly pyrolysis. Then HCC and PCC were immobilized on the surface of screen printed carbon electrodes (SPCE), fabricating HCC and PCC modified electrodes (denoted as HCC/SPCE and PCC/SPCE). HCC/SPCE, best operated at −0.5 V (vs. Ag/AgCl), has a sensitivity of 6.55 × 10 2  nA μM −1  cm −2 with a detection limit of 207 nM (at S/ N  = 3) for O 2 •− sensing. And PCC/SPCE, best operated at −0.4 V (vs. Ag/AgCl), exhibited a superior performance for O 2 •− detection with a sensitivity of 1.14 × 10 3  nA μM −1  cm −2 and a low detection limit of 140 nM (at S/ N  = 3). The two sensors possess excellent reproducibility and stability. They were used to sense O 2 •− released from HeLa cells. Illustration of the synthesis of the hollow carbon cubic nanomaterial (HCC) and of the porous carbon cubic nanomaterial (PCC), and the scheme for detection of superoxide anions in HeLa cell.

研究领域: 材料科学 · 生物化学 · 分析化学 · 纳米技术
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RSC Advances · 2018 ·Vol. 8 ·期 33 ·18266-18271 · IF 2.936

Rapid quantitation of multiple ions released from HeLa cells during emodin induced apoptosis by low-cost capillary electrophoresis with capacitively coupled contactless conductivity detection

Jing Zhang,Xuan Wei,Yuanhang Wang,Bo Ren,Litao Zhao,Zhaoyan Wang,Qiaosheng Pu

Change in cation concentration, including that of potassium and sodium, is characteristic of apoptosis, therefore it is significant to detect cation concentration changes. In this work a rapid, sensitive, and practical method was developed for the determination of Na+ and K+ concentration in HeLa cells during emodin induced apoptosis by a low-cost capillary electrophoresis device with capacitively coupled contactless conductivity detection (CE-C4D). Under the optimized conditions, both ions were baseline separated in 4 min with 40 mM MES/40 mM His containing 1 mM 18-crown-6 as the separation buffer at pH 6.0. The limit of detections (LODs) and limit of quantifications (LOQs) were 0.47–1.15 μM and 1.58–3.86 μM, respectively. The precision for migration times and peak areas was below 0.56% and 3.74%, respectively. The data proved that the concentration of cations in cells can be accurately quantified. It was found that the K+ concentration decreased from 82.2 μM to 52.7 μM, and the Na+ concentration increased from 62.4 μM to 127.2 μM during the process of apoptosis when the cell density was 1 × 105 cells per mL. The low-cost CE-C4D provides a convenient way to decipher the interaction of Na+ and K+ in the regulation of cell apoptosis.

研究领域: 分析化学 · 生物化学 · 细胞生物学 · 药理学
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Science of Advanced Materials · 2022 ·Vol. 14 ·期 5 ·911-919 · IF 1.067

Research on Mechanism of FePt Nanoparticles at Varied Concentrations in Regulating DNA Injury and Inactivation of Hela Cells Through Mitogen-Activated Protein Kinase Signal Pathway

Zhu Chunxia,Ming Shenqiu,Qiu Bin,Zhong Hui

FePt nanoparticles were in this study prepared at varied concentrations to assess their mechanism in regulating DNA injury and inactivation of Hela cells through mitogen-activated protein kinase (MAPK) signal pathway. The cells were divided into following 5 group sets: 1st, 2nd, 3rd, 4th and 5th, which were randomly intervened by following varied concentrations of FePt nanoparticles; 0, 5, 10, 15 and 20 μg/mL. Their action on cellular toxicity, proliferation and inactivation of cells was detected with CCK-8 method, while apoptotic condition was detected with flow cytometry (FCM). The degree of DNA double chains fracture was detected with neutral single cell gel electrophoresis and immunofluorescence staining. The protein expressions of of EKR1/2, p-ERK1/2, p38 MAPK and p-p38 MAPK in every set were detected with Western Blot assay, while proliferative activity in the 4th and 5th sets was lower than in the 1st set, and inhibiting action in the 4th set was best. There was no notable difference between 4th and 5th sets, and apoptotic rate in the 1st set was lower than in the other sets. The DNA percentage in the Hela cells was reduced and Tial length was lengthened along with increased concentration of adopted FePt nanoparticles. The proliferation of Hela cells was restrained by FePt nanoparticles through restraining of the MAPK signal pathway, but growth of Hela cells was not affected, and DNA double-strand break (DSB) was increased. The FePt nanoparticles could therefore be adopted as one kind of effective anti-tumor drug through increased DNA DSB in tumor cells based on killing effect of tumor cells and good compatibility for normal cells.

研究领域: 纳米技术 · 癌症生物学 · 细胞信号传导 · 毒理学
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Nanotoxicology · 2023 · IF 5

Enhanced toxicity of 2,2-bis(chloromethyl) trimethylene bis[bis(2-chloroethyl) phosphate] (V6) by nanopolystyrene particles towards HeLa cells

Zheng Zhong,Xin Liu,Yiming Ruan,Ziwei Li,Junxian Li,Lili Sun,Sen Hou

2,2-bis(chloromethyl) trimethylene bis[bis(2-chloroethyl) phosphate] (V6) has been widely used as an additive in a variety of plastics due to its extremely low toxicity. However, we showed in the study that once mixed with nanopolystyrene particles (NPs), the nontoxic V6 could exhibit significant toxicity to HeLa cells. The enhanced toxicity was much higher than the toxicity of NPs alone and was related to the size of NPs. The mixture of V6 and small polystyrene NPs (10 nm and 15 nm in radius) showed obvious toxicity to HeLa cells. The toxicity increased with the concentrations of both V6 and NPs. On the contrary, the mixture of V6 and larger NPs (25 nm, 50 nm, 100 nm, and 500 nm in radius) showed almost no toxicity even at extremely high concentrations (NPs: 100 mg/L; V6: 50 mg/L). The small NPs could enter the cells and accumulated in cytoplasm. However, the larger NPs did not distribute inside the cells. NPs efficiently adsorbed V6 on the surface. The mechanism of the enhanced toxicity was attributed to the increased intracellular reactive oxygen species (ROS) production and the regulation of gene expression concerning apoptosis and ROS scavenging. Our study not only showed that a safe chemical V6 could be turned to be toxic by NPs, but also pointed out a potential risk caused by the joint toxicity of ‘safe’ chemicals and plastic particles with small size.

CAS / MDL: 67-68-5 7758-02-3
研究领域: 毒理学 · 细胞生物学 · 环境科学
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JOURNAL OF CHEMICAL SCIENCES · 2020 ·Vol. 132 ·期 1 ·1-10 · IF 1.406

Colorimetric sensing platform based on MnO2 nanosheets for the detection of reducing substances and alkaline phosphatase activity in whole Hela cells

Zhao Lingzhi

Abstract The development of efficient methods for alkaline phosphatase (ALP) activity assay is of great importance in clinical diagnosis and many biomedical applications. In this work, the authors create two strategies for colorimetric detection of ALP activity. The first strategy is developed by using directly manganese dioxide (MnO 2 ) nanosheets as colorimetric probes. The second strategy is developed by using MnO 2 and the chromogenic substrate 3,3′,5,5′-tetramethylbenzidine (TMB) as colorimetric probes based on the catalytic reduction of oxidized TMB. The first strategy has a linear response in 10 U L −1 to 80 U L −1 with 3.0 U L −1 detection limit while the second one has a linear response in 7 U L −1 to 100 U L −1 with 0.05 U L −1 detection limit. The method based on MnO 2 -TMB which have lower detection limit and higher sensitivity was applied to monitor ALP activity in whole Hela cells lysate. In addition, based on redox properties, MnO 2 -TMB sensing system was successfully used in detecting reducing substances such as ascorbic acid, Na 2 S and so forth. Conceivably, MnO 2 -TMB sensing system is not limited to ALP activity assay but has a wide scope to be applied in assays of the total antioxidant capacity of dietary substances and biological fluids. Graphic Abstract Two strategies were created for colorimetric detection of ALP activity: The first strategy is developed by using directly manganese dioxide (MnO 2 ) nanosheets as colorimetric probes, and the second strategy by using MnO 2 and the chromogenic substrate 3,3′,5,5′-tetramethylbenzidine (TMB) as colorimetric probes based on the catalytic reduction of oxidized TMB.

研究领域: 分析化学 · 生物化学 · 生物医学工程 · 临床诊断
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ANALYST · 2018 ·Vol. 143 ·期 17 ·4199-4205 · IF 3.864

An electrochemiluminescence cytosensor for sensitive detection of HeLa cells based on a signal amplification strategy of Au-NaYF4:Yb,Er nanocomposites

Jinzha Zhang,Yang Shen,Yuhong Liu,Zaiying Hou,Yuanqing Gu,Wenbo Zhao

A novel electrochemiluminescence (ECL) cytosensor was proposed for the quantitative detection of HeLa cells (human cervical cancer cells) with the help of a signal amplification strategy. Firstly, the Au-NaYF4:Yb,Er nanocomposites were prepared by a simple in situ hydrothermal method and characterized by transmission electron microscopy (TEM) images, X-ray diffraction (XRD) patterns, UV-vis spectra and Fourier transform infrared (FTIR) spectra. Compared with the bare NaYF4:Yb,Er nanocomposites, the ECL intensity of Au-NaYF4:Yb,Er nanocomposites was greatly enhanced by about 4.2-fold which can be attributed to the good conductivity of gold nanoparticles (Au NPs). The nanocomposites showed high and stable ECL emission, fast response and superior conductivity, all of which were advantageous to the ECL detection. Furthermore, HeLa cells were immobilized on the modified electrode via the interaction between folic acid and a folate receptor present on the cell surface. The ECL cytosensor showed satisfactory sensitive response to HeLa cells in a linear range of 4.25 × 102–4.25 × 105 cells per mL with a low detection limit of 326 cells per mL. The proposed cytosensor had good sensitivity and stability, which can offer a great potential platform for bioassay analysis.

研究领域: 分析化学 · 生物传感器 · 纳米技术 · 癌症研究
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Journal of Materials Chemistry B · 2018 ·Vol. 7 ·期 3 ·401-407 · IF 4.776

Carbon-mediated synthesis of shape-controllable manganese phosphate as nanozymes for modulation of superoxide anions in HeLa cells

Xuan Cai,Zhenxing Wang,Huanhuan Zhang,Yufei Li,Kaicha Chen,Hongli Zhao,Minbo Lan

Transition metal phosphates have shown great potential as nanozymes for selective detection of reactive oxygen species (ROS), but its application has been hindered by the complicated synthesis and difficulty in shape and size control. Herein, we present a facile method to fabricate transition metal phosphates by using hollow carbon structures as substrates. Manganese phosphate is a typical Nanozyme used in this design and the shape and size of the Mnx(PO4)y layer can be efficiently controlled by altering the carbon substrates. Characterization demonstrated that Mnx(PO4)y layer modified hollow carbon sphere (Mn-MPSA-HCS) and hollow carbon cubic (Mn-MPSA-HCC) were successfully prepared and used as nanozymes for superoxide detection. The established electrochemical sensor was employed in the online monitoring of drug stimulated superoxide anions released from cancer cells. This method can be adapted as a general way to prepare transition metal phosphate layers with various controllable shapes and sizes as nanozymes for different uses in the future.

研究领域: 材料科学 · 纳米技术 · 生物化学 · 癌症研究
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CHEMICO-BIOLOGICAL INTERACTIONS · 2022 · IF 5.168

Fenbendazole and its synthetic analog interfere with HeLa cells’ proliferation and energy metabolism via inducing oxidative stress and modulating MEK3/6-p38-MAPK pathway

Yi Peng,Jie Pan,Fengting Ou,Wenchao Wang,Haihong Hu,Lu Chen,Su Zeng,Kui Zeng,Lushan Yu

Fenbendazole, a broad-spectrum anti-parasitic drug, can be a potential anti-tumor agent. In this study, we synthesized and purified its derivative, analog 6, intending to achieve improved efficacy in cancer cells and decreased toxicity in normal cells. To evaluate in vitro anti-tumor activities of fenbendazole and analog 6 in different cancer cell lines, a CCK-8 assay was performed, and we found that human cervical cancer HeLa cells were more sensitive to analog 6 than to fenbendazole. Furthermore, we explored the associated mechanism, and our results showed that analog 6 and fenbendazole could induce oxidative stress by accumulating ROS . It not only activated the p38-MAPK signaling pathway, thereby inhibiting the proliferation of HeLa cells and enhancing the apoptosis of HeLa cells, but also significantly induced impaired energy metabolism and restrained their migration and invasion. In addition, the modified analog 6 showed reduced toxicity to normal cells without decreased anti-cancer effect. In conclusion, fenbendazole and analog 6 have multiple targets and strong anti-tumor effects on HeLa cells in vitro and in vivo . The optimized analog 6 could inhibit the viability of HeLa cells with lower toxicity than normal human cells, promising to be developed as an antitumor active compound.

研究领域: 肿瘤学 · 细胞生物学 · 药理学
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Biomaterials Science · 2019 ·Vol. 8 ·期 1 ·201-211 · IF 5.251

Polyethyleneimine coated Fe3O4 magnetic nanoparticles induce autophagy, NF-κB and TGF-β signaling pathway activation in HeLa cervical carcinoma cells via reactive oxygen species generation

Shuli Man,Miao Li,Jin Zhou,Haiyue Wang,Jinyan Zhang,Long Ma

Fe3O4 magnetic nanoparticles (MNPs), as one of the most intensively researched NPs, have a range of applications in cancer treatments. In current research, we have focused on the influences of MNPs on cancer cells. We chose polyethyleneimine (PEI) coated MNPs (PEI-MNPs) as a model and they are colloidally stable in biological media. It can be proved that PEI-MNPs result in autophagy induction via mTOR-Akt-p70S6 K and ATG7 signaling pathways. For the first time, we have reported that PEI-MNPs activate both NF-κB and TGF-β signaling, two key pro-inflammatory pathways, in cancer cells. More significantly, we have found that autophagy induction and NF-κB and TGF-β activation can be efficiently suppressed through the inhibition of PEI-MNP dependent reactive oxygen species (ROS) over-production. ROS are deemed as a ‘double edge sword’ for cancer cells, owing to the cancer-suppressing and cancer-promoting actions. Our findings would be useful for designing MNPs induced ROS anti-cancer strategies or diminishing long-term toxic effects.

CAS / MDL: 30827-99-7 498-02-2
研究领域: 纳米技术 · 癌症生物学 · 细胞信号传导 · 药理学
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POLYMER BULLETIN · 2019 ·Vol. 77 ·期 2 ·963-974 · IF 1.858

Plasma-initiated polymerization of N-isopropylacrylamide and functionalized with dopamine for the adhesion to Hela cells

Yang Xu,Sun Zhaojie,Gao Jingru,Yang Chunhui,Tang Dongyan

Temperature-responsive films of poly( N -isopropylacrylamide) (PNIPAM) were facilely fabricated by one-step plasma-initiated polymerization and then functionalized by self-polymerization of dopamine on the surface. High retention of the monomer structure and temperature-responsive properties in PNIPAM films were confirmed. After plasma-initiated polymerization, PNIPAM films formed protrusions and ridges surfaces. Moreover, cross-linker of N , N ′-methylenebisacrylamide with different dosage was introduced into the systems to effectively modulate the roughness of PNIPAM films and to supply better adhesive surface. Furthermore, in cell culture, satisfactory survival rate of the attached Hela cells was obtained on PNIPAM films, and the cell viability was improved further on PNIPAM/PDA films. The results indicated that such films might be applicable in medical treatment and tissue engineering, due to their adjusted adhesion ability and less toxicity to cells.

研究领域: 材料科学 · 生物材料 · 细胞生物学 · 组织工程
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