Experimental and Therapeutic Medicine
·
2019
·Vol. 18
·期 3
·1793-1799
·
IF 1.448
Huijuan Zhai,Teng Pan,Haiyan Yang,Haiyu Wang,Yadong Wang
Cadmium (Cd) is an established carcinogen that is involved in the progression of lung cancer. However, the mechanisms underlying this Cd‑induced process have yet to be fully elucidated. The present study explored the potential roles of phosphorylated (p)‑ERK in the Cd‑induced migration and invasion of lung cancer cells. An MTT assay was performed to evaluate cell viability whilst western blot analysis and reverse transcription‑quantitative PCR were used to detect the expression of protein and mRNA, respectively. Migration and invasion assays were performed to assess cell migratory and invasive abilities. The results demonstrated that exposure to Cd increased the expression of p‑ERK in A549 cells. Cd also enhanced the migration and invasion of A549 cells, which could be blocked via U0126 treatment (an inhibitor of mitogen activated protein kinase). In addition, it was identified that Cd‑induced expression of matrix metalloproteinases 2 mRNA was mediated by p‑ERK. In conclusion, the present findings indicated that Cd induced A549 cell migration and invasion by activating ERK, and it was hypothesized that p‑ERK could serve as a target in the clinical treatment of Cd‑induced lung cancer.
研究领域:
肿瘤学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
eFood
·
2022
·Vol. 3
·期 3
·e13
·
IF 0
Hui Cao,Petra Högger,Miguel-Angel Prieto,Jesus Simal-Gandara,Jianbo Xiao
Quercetin is evidently unstable in Dulbecco's modified Eagle's medium (DMEM) at 37°C. However, the underlying mechanism of this instability is not clear yet. The stability and new degradation products of quercetin in DMEM at 37°C were investigated via in UPLC-MS-MS analysis. With increasing incubation time, quercetin formed various degradation products derived from its dimer and there were numerous isomers formed during this process. Ascorbic acid significantly improved the stability of quercetin by protecting quercetin from auto-oxidation in this medium. Ascorbic acid also remarkably enhanced the stability of quercetin in DMEM in the presence of A549 cells and obviously increased the antiproliferative effect of quercetin toward A549 cells.
研究领域:
药理学
·
细胞生物学
✓ 已验证
DOI
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2017
·
IF 3.671
Jun Wu,Weiping Gao,Zhuoyue Song,Qingping Xiong,Yingtao Xu,Yun Han,Jun Yuan,Rong Zhang,Yunbo Cheng,Jiansong Fang,Weirong Li,Qi Wang
The purpose of this study was to investigate the anticancer activity of polysaccharide (PGL) from Glehnia littoralis on human lung cancer cell line A549. Based on MTT assay, the results suggested that PGL could significantly reduce A549 cells proliferation in a time- and dose-dependent manner. In addition, PGL displayed an inhibitory activity for the A549 cells migration in Transwell migration assay. The results from both flow cytometry analysis and Hochst 3342 staining of apoptotic cells indicated that PGL could promote apoptosis, and induce cycle arrest of A549 cells. Moreover, immunofluorescence assay elucidated PGL could also down-regulate expression of proliferating cell nuclear antigen (PCNA). Overall, these results showed that PGL exerts a strong anticancer action through inhibiting the A549 cells migration, proliferation and inducing cell apoptosis. It could be a new source of natural anticancer agent against lung cancer with potential value in supplements and medicine.
研究领域:
药理学
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肿瘤学
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植物化学
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DOI
PubMed
高影响因子
JOURNAL OF APPLIED TOXICOLOGY
·
2018
·Vol. 38
·期 11
·1437-1446
·
IF 2.909
Wen-jie Zhao,Zi-jin Zhang,Zhen-yu Zhu,Qun Song,Wei-juan Zheng,Xin Hu,Li Mao,Hong-zhen Lian
Cadmium is considered one of the most harmful carcinogenic heavy metals in the human body. Although many scientists have performed research on cadmium toxicity mechanism, the toxicokinetic process of cadmium toxicity remains unclear. In the present study, the kinetic response of proteome in/and A549 cells to exposure of exogenous cadmium was profiled. A549 cells were treated with cadmium sulfate (CdSO 4 ) for different periods and expressions of proteins in cells were detected by two-dimensional gel electrophoresis. The kinetic expressions of proteins related to cadmium toxicity were further investigated by reverse transcription-polymerase chain reaction and western blotting. Intracellular cadmium accumulation and content fluctuation of several essential metals were observed after 0–24 hours of exposure by inductively coupled plasma mass spectrometry. Fifty-four protein spots showed significantly differential responses to CdSO 4 exposure at both 4.5 and 24 hours. From these proteins, four expression patterns were concluded. Their expressions always exhibited a maximum abundance ratio after CdSO 4 exposure for 24 hours. The expression of metallothionein-1 and ZIP-8, concentration of total protein, and contents of cadmium, zinc, copper, cobalt and manganese in cells also showed regular change. In synthesis, the replacement of the essential metals, the inhibition of the expression of metal storing protein and the activation of metal efflux system are involved in cadmium toxicity.
研究领域:
毒理学
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细胞生物学
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蛋白质组学
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产品关联
DOI
PubMed
高影响因子
BIOLOGICAL TRACE ELEMENT RESEARCH
·
2014
·Vol. 159
·期 1
·393-398
·
IF 1.608
Jin Chan,Wang Fude,Tang Ying,Zhang Xiangzhi,Wang Jianqiang,Yang Yongji
Graphene and its derivatives are increasingly applied in nanoelectronics, biosensing, drug delivery, and biomedical applications. However, the information about its cytotoxicity remains limited. Herein, the distribution and cytotoxicity of graphene oxide (GO) and TiO 2 -graphene oxide composite (TiO 2 -GO composite) were evaluated in A549 cells. Cell viability and cell ultrastructure were measured. Our results indicated that GO could enter A549 cells and located in the cytoplasm and nucleus without causing any cell damage. TiO 2 nanoparticles and GO would be separated after TiO 2 -GO composite entered A549 cells. TiO 2 -GO composite could induce cytotoxicity similar to TiO 2 nanoparticles, which was probably attributed to oxidative stress. These results should be considered in the development of biological applications of GO and TiO 2 -GO composite.
研究领域:
纳米技术
·
生物医学工程
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毒理学
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产品关联
DOI
PubMed
高影响因子
Cancer Management and Research
·
2020
·
IF 2.886
Jun Sha,Dandan Cao,Rui Cui,Lu Xia,Xin Hua,Yuan Lu,Shuhua Han
Introduction Mannose, a major monosaccharide component of N-glycans, involves in the glycometabolism of human body. Recently, mannose has been shown to suppress tumor growth through enhancing chemosensitivity and reducing the activity of mannose phosphate isomerase (MPI). However, it is largely unknown whether mannose exerts effects on non-small cell lung cancer (NSCLC). Materials and Methods First, a mannose IC50 assay was conducted to find a suitable concentration of mannose for cell experiments. Then, vitro studies including CCK-8 assay, scratch wound healing assay, and TUNEL assay were performed to evaluate the effects of mannose on A549 cells, and an animal model was established to evaluate the antitumoural effect of mannose on NSCLC in vivo. Finally, immunohistochemistry was done to detect the expression of MPI by Rabbit Anti-MPI. Results In this study, a concentration of mannose, 15mM, was used to explore the suppressive effect of mannose on A549 cells. CCK-8 assay demonstrated that mannose significantly inhibited the proliferation of A549 cells and enhanced the anti-tumor efficacy of carboplatin. Wound healing assay showed that mannose inhibits the migration of A549 cells, and mannose-induced migration inhibition was more efficient in A549 cells treated with carboplatin. TUNEL assay demonstrated that mannose significantly enhanced the efficacy of carboplatin to promote apoptosis treated by mannose (15mM) or carboplatin. The results of animal experiments revealed that the size and weight of tumors derived from A549 cells treated with mannose were smaller than those derived from control cells, and co-treatment with mannose and carboplatin had most efficient inhibition on tumor growth. MPI expression detection showed that the expression level of MPI in the stage Tis (tumor in situ) was the highest, while the stage IV has the lowest. Discussion Collectively, our findings suggest that mannose inhibited cell proliferation and migration, promoted cell apoptosis and enhanced the efficacy of carboplatin in lung adenocarcinoma. Preliminary results showed that mannose had less side effect on health. In the future, mannose may be a potential candidate drug for adjuvant therapy of lung adenocarcinoma.
研究领域:
肿瘤学
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药理学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2023
·
IF 5.2
Hailiang Chen,Chenyu Liu,Simiao Yu,Hengjun Zhou,Farishta Shafiq,Weihong Qiao
The emergence of liposomes has provided a breakthrough for the clinical use of highly toxic chemotherapeutic drugs . However, the clinical effects of conventional drug-loaded liposomes are unsatisfactory due to the lack of specific targeting of cancer cells and the inability to achieve endosome escape and controllable release in vivo. In this paper, a cRGD-PEOz-Hz-DOB (cPzD) molecule with specific targeting, endosomal escape, and endogenous acid-sensitive controlled release ability was creatively designed and synthesized to prepare drug-loaded liposomes cPzDGX encapsulating the anticancer drug Doxorubicin (DOX) in order to enhance the anticancer performance of DOX. The study found that the hydrazone bond in cPzD reached a breakage rate of 42% within 48 h at pH 5.0, so the cumulative release rate of cPzDGX at pH 5.0 for 48 h was as high as 82.9%, which was 22.5% higher than that at pH 7.4. Moreover, the uptake of cPzDGX in A549/ADR cells was increased by 62% at 2 h, and the expression of the green fluorescent protein gene EGFP was also increased by 36% relative to the targeting control group, indicating that cRGD modification could effectively improve the targeting ability of liposomes to cancer cells. In addition, it was demonstrated that PEOz modification could help drug carriers achieve endosome escape because the green fluorescent protein expression in the PEOz-modified liposome group was 60.5% higher than that in the PEG-modified group. Finally, the cell viability of the cPzDGX group decreased by 17.2% relative to the free DOX group when the DOX concentration was 1 μg/mL in the cytotoxicity assay, and the diameter reduction of 3D tumor MCs increased by 34.4%. And cPzDGX could effectively enhance the permeability of free DOX to solid tumors. The above results indicate that the DOX-loaded liposomes cPzDGX we designed have great prospects for the accurate and efficient treatment of cancer.
研究领域:
肿瘤学
·
药剂学
·
生物化学
✓ 已验证
产品关联
DOI
高影响因子
PHARMACEUTICAL BIOLOGY
·
2016
·
IF 1.546
Huihui Yuan,Bo Sun,Feng Gao,Minbo Lan
Context: Paclitaxel (PTX) is widely used in chemotherapy for cancer treatment; however, it has some serious side effects. Andrographolide (Andro) is a potential cancer therapeutic agent isolated from Andrographis paniculata (Burm. f.) Nees (Acanthaceae).Objective: The objective of this study is to evaluate the effects of PTX combined with Andro against A549 cells.Materials and methods: The effects of 24–48 h treatment with 0.48–60.75 nM PTX and 5.10–328.0 μM Andro on cellular proliferation, apoptosis, cell cycle and intracellular reactive oxygen species (ROS) were determined by sulphorhodamine B assay, Annexin V-FITC/PI apoptosis detection, PI staining and ROS assay, respectively. Synergy was determined using combination index. The antitumour efficacy of 20 mg/kg PTX with 100 mg/kg Andro was studied in a xenograft murine model.Results: IC50 value of the PTX combined with Andro against A549 cells was 0.5–7.4 nM, which was significantly lower than that of PTX (15.9 nM). PTX with 10 μM Andro caused (1.22–1.27)-fold apoptosis and 1.7-fold ROS accumulation compared with PTX alone. N-Acetylcysteine, a ROS scavenger, blocked this synergy in vitro. In contrast, G2/M phase cell cycle arrest resulting from PTX was not potentiated by Andro. Moreover, PTX in combination with Andro inhibited the growth of A549 transplanted tumours by 98%.Discussion and conclusion: The results indicate that the combination of PTX and Andro exert significant synergistic anticancer effect on A549 cells in vitro and in vivo. The synergy may be the result of the accumulation of ROS. The combination of Andro and PTX represents a potential strategy for the treatment of A549 cells.
研究领域:
肿瘤学
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药理学
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分子生物学
·
癌症研究
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2022
·
IF 7.033
Xiaorui Shi,Xinan Wang,Rong Huang,Chu Tang,Chong Hu,Pengbo Ning,Fu Wang
Background: Micro- and nano-sized plastics (MPs and NPs) have become an environmental issue of global concern due to their small size, strong bio-permeability and high specific surface area. However, few studies have assessed the effect of polystyrene MPs and NPs on human lung cells. In this research, we evaluated the cytotoxicity and genotoxicity of polystyrene (PS) MPs and NPs with different sizes (2 μm and 80 nm) and surface modification (carboxy and amino functionalized polystyrene, pristine polystyrene) in A549 cells. Methods: The zeta potential and hydrodynamic particle size of five types of PS plastic solutions were measured by dynamic light scattering, and their morphology and degree of aggregation were observed by scanning electron microscopy. After incubation of the PS plastics with A549 cells, the uptake and toxicity of the cells were assessed by fluorescence microscopy, laser scanning confocal microscopy, flow cytometry, MTT, micronucleus formation assay, and reactive oxygen species. Results: The cytotoxicity and genotoxicity of A549 cells caused by nano-level PS is more serious than that of micro-level. Compared with unmodified PS-NPs, more surface-functionalized PS-NPs were found inside the cells, especially the accumulation of PS-NH 2 . Cell viability and the induction of micronuclei (MN) are appreciably impacted in a dose-dependent way. Compared with pristine PS-NPs, functionalized PS-NPs showed stronger cell viability inhibitory ability, and induced more MN scores. Conclusion: This study shows that the intrinsic size properties and surface modification of PS plastics, the interaction between PS plastics and the receiving medium, intracellular accumulation are critical factors for evaluating the toxicological influences of PS plastics on humans.
研究领域:
环境科学
·
毒理学
·
生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
STAR Protocols
·
2024
·
IF 1.3
Jiahui Huang,Yao Zhang,Shuo Sheng,Lian-Hui Zhang,Zeling Xu
Summary Pseudomonas aeruginosa utilizes a type III secretion system (T3SS) to directly inject effector proteins into host cells, leading to severe acute infections. Here, we present a protocol for detecting the T3SS-mediated cytotoxicity of P. aeruginosa using the A549 cell line. We describe the steps for the preparation of the A549 cell line and P. aeruginosa strains, cell seeding, bacterial culture, infection, and cytotoxicity assay. Additionally, we provide detailed procedures for data analysis. For complete details on the use and execution of this protocol, please refer to Huang et al. 1
研究领域:
微生物学
·
细胞生物学
·
传染病学
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY AND INDUSTRIAL HEALTH
·
2024
·
IF 1.7
Shuang Chen,Chengzhi Liu,Yifan Yang,Jiangliang Chu,Beilei Yuan,Zhe Wang
Silica nanoparticles (SiNPs) are widely utilized in occupational settings where they can cause lung damage through inhalation. The objective of this research was to explore the metabolic markers of SiNPs-induced toxicity on A549 cells by metabolomics and provide a foundation for studying nanoparticle-induced lung toxicity. Metabolomics analysis was employed to analyze the metabolites of SiNPs-treated A549 cells. LASSO regression was applied for selection, and protective measure experiments were conducted to validate the efficacy of selected potential toxicity mitigators. After SiNPs treatment, 23 differential metabolites were identified, including lipids, nucleotides, and organic oxidants. Pathway analysis revealed involvement in various biological processes. LASSO regression further identified six metabolites significantly associated with SiNPs toxicity. Notably, phosphatidylethanolamine (PE (14:1(9Z)/14:0)) showed enrichment in six significant metabolic pathways and with an AUC of 1 in the ROC curve. Protective measure experiments verified its protective effect on A549 cells and demonstrated its considerable inhibition of SiNPs-induced cytotoxicity. This study elucidated SiNPs-induced cytotoxicity on A549 cells and identified PE as a potential toxicity mitigator. These findings contribute to understanding the mechanisms of nanoparticle-induced lung toxicity and inform occupational health preventive strategies.
研究领域:
毒理学
·
生物化学
·
职业健康
✓ 已验证
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2019
·
IF 4.18
Dan Chen,Ya-Xian Wu,Yu-bao Qiu,Bin-bin Wan,Gang Liu,Jun-liang Chen,Mu-dan Lu,Qing-feng Pang
Background Hypoxia is commonly existed in tumors and lead to cancer cell chemo/radio-resistance. It is well-recognized that tumor hypoxia is a major challenge for the treatment of various solid tumors . Hyperoside (quercetin-3-O-galactoside, Hy) possesses antioxidant effects and has been reported to protect against hypoxia/reoxygenation induced injury in cardiomyocytes . Therefore, Hy may be attractive compound applicable to hypoxia-related diseases . Purpose This study was designed to determine the role of Hy in hypoxia-induced proliferation of non-small cell lung cancer cells and the underlying mechanism. Study Design and Methods A549, a human non-small cell lung cancer (NSCLC) cell line, was used in the present study. 1% O 2 was used to mimic the in vivo hypoxic condition of NSCLC. The potential mechanisms of Hy on hypoxia-induced A549 survival and proliferation, as well as the involvement of AMPK/HO-1 pathway were studied via CCK-8 assay, EdU staining, flow cytometry, qRT-PCR and western blot . Results We showed that pretreatment with Hy suppressed hypoxia-induced A549 survival and proliferation in dose-dependent manner. In terms of mechanism, hypoxia-treated A549 showed the lower AMPK phosphorylation and the reduced HO-1 expression, which were reversed by Hy pretreatment. Both AMPK inhibitor (Compound C) and HO-1 activity inhibitor (Zinc protoporphyrin IX) abolished Hy-evoked A549 cell death under hypoxia stimuli. Of note, Ferrous iron contributed to Hy-induced A549 cell death under hypoxia, while Hy had no effect on lipid peroxidation under hypoxia. Conclusion Taken together, our results highlighted the beneficial role of Hy against hypoxia-induced A549 survival and proliferation through ferrous accumulation via AMPK/HO-1 axis.
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
危险品化学品经营许可证（带存储）