scholarly journals Anticancer Effects of Auranofin in Human Lung Cancer Cells Through Increasing Intracellular ROS Levels and GSH Depletion

2021 ◽  
Author(s):  
Sun Hyang Park ◽  
Xia Ying Cui ◽  
Woo Hyun Park
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cell Death ◽  
Cancer Cells ◽  
Cancer Cell ◽  
A549 Cells ◽  
Thioredoxin Reductase ◽  
Lung Cancer Cells ◽  
Blue Staining ◽  
Lung Cancer Cell

Abstract Purpose Auranofin is known to inhibit thioredoxin reductase (TrxR) and has promising anticancer activity in several cancer types. However, at present, there is no clear explanation for the mechanism underlying the inhibitory effects of Auranofin on lung cancer cell growth. In this study, we evaluated the antigrowth effects of Auranofin in cells from various lung cancer cell lines with regard to cell death, reactive oxygen species (ROS), and glutathione (GSH) levels.Methods Cell proliferation was assessed using the trypan blue staining cell counting. ROS levels including O2·-, GSH levels, and MMP (∆Ψm) loss were measured using a flow cytometry. Apoptosis was determined with annexin V-PI staining assay and the change of apoptosis-related protein level was detected by western blotting. TrxR activity was evaluated using a thioredoxin reductase colorimetric assay kit.Results Treatment with Auranofin inhibited cell proliferation and induced cell death based on cell number at 24 h in Calu-6, A549, SK-LU-1, NCI-H460, and NCI-H1299 cells. In addition, Auranofin led to increased ROS levels including O2·- and GSH depletion in these cells. Treatment with N-acetyl cysteine (NAC) attenuated the growth inhibition, mitochondrial membrane potential (MMP, ∆Ψm) loss, and increased ROS levels and GSH depletion in Auranofin-treated Calu-6 and A549 cells. By contrast, L-buthionine sulfoximine (BSO) enhanced cell death, MMP (∆Ψm) loss, ROS production, and GSH depletion. Furthermore, the western blot analysis indicated that Auranofin-induced caspase-3 activation and poly (ADP ribose) polymerase (PARP) cleavage, both of which were prevented by pretreatment with NAC but enhanced by pretreatment with BSO in Calu-6 and A549 cells. Consistent with these changes, the decrease in TrxR activity caused by Auranofin was enhanced by preincubation with BSO and restored in response to the preincubation with NAC in both Calu-6 and A549 cells.Conclusion Our present findings demonstrate that Auranofin-induced cell death is tightly related to oxidative stress in lung cancer cells.

scholarly journals Rose (Rosa gallica) Petal Extract Suppress Proliferation, Migration, and Invasion of Human Lung Adenocarcinoma A549 Cells through via the EGFR Signaling Pathway

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5119
Author(s):  
Won-Chul Lim ◽  
Hyo-Kyung Choi ◽  
Kyung-Tack Kim ◽  
Tae-Gyu Lim
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Matrix Metalloproteinase ◽  
Cancer Cells ◽  
Cancer Cell ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
Egfr Signaling Pathway ◽  
Rosa Gallica

We sought to investigate the effect of rose petal extract (RPE) on the proliferation, migration, and invasion of cancer cells. RPE significantly inhibited the growth of lung and colorectal cancer cell lines, with rapid suppression of A549 lung cancer cells at low concentrations. These effects occurred concomitantly with downregulation of the cell proliferation mediators PCNA, cyclin D1, and c-myc. In addition, RPE suppressed the migration and invasion of A549 cells by inhibiting the expression and activity of matrix metalloproteinase-2 and matrix metalloproteinase-9 (MMP-2 and -9). We hypothesize that the suppressive activity of RPE against lung cancer cell proliferation and early metastasis occurs via the EGFR-MAPK and mTOR-Akt signaling pathways. These early results highlight the significant potency of RPE, particularly for lung cancer cells, and warrant further investigation.

scholarly journals USP46 inhibits cell proliferation in lung cancer through PHLPP1/AKT pathway

2020 ◽  
Author(s):  
Wei Wang ◽  
Meng Chen ◽  
Hailing Xu ◽  
Dongqing Lv ◽  
Suna Zhou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Lung Cancer Cells ◽  
Akt Pathway ◽  
Cancer Cell Proliferation ◽  
Lung Cancer Cell ◽  
Knock Down

Abstract Background: USP46 has been shown to function as tumor suppressor in colon cancer and renal cell carcinoma. However, its specific role in other cancers remains unknown. This study was aimed to investigate the role of USP46 in lung cancer tumorigenesis, and to identify the underlying mechanism. Methods: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western Blotting (WB) were used to measure the expression levels of USP46 and PHLPP1 in lung cancer tissue and adjacent normal tissue from lung cancer patients. The functional role of USP46 in regulating proliferation in lung cancer cells were examined by cell proliferation assay, radiation assay, genetic overexpression and knock down and chemical inhibition of relevant genes. The underlying mechanisms were investigated in multiple lung cancer cell line models by co-immunoprecipitation and ubiquitination assays. Results: This study identified strong downregulation of USP46 and PHLPP1 expression in lung cancer tissues relative to normal adjacent tissues. USP46 was further shown to inhibit lung cancer cell proliferation under normal growth conditions and during radiation induced DNA damage by antagonizing the ubiquitination of PHLPP1 resulting in the inhibition of AKT signaling. The effect of USP46 knock down on lung cancer cell proliferation was significantly reversed by exposure to radiation and AKT inhibition. Conclusions: USP46 is down-regulated in lung cancer, and it suppresses proliferation of lung cancer cells by inhibiting PHLPP1/AKT pathway. AKT inhibition slows proliferation of USP46 down-regulated lung cancer cells exposed to radiation suggesting a potential therapeutic avenue for USP46 down-regulated lung cancer through a combination of radiation and AKT inhibitor treatment.

Fluorinated thiazolidinols cause cell death in A549 lung cancer cells via PI3K/AKT/mTOR and MAPK/ERK signalling pathways

MedChemComm ◽  
2016 ◽  
Vol 7 (6) ◽  
pp. 1197-1203 ◽  
Author(s):  
Ravindra M. Kumbhare ◽  
Tulshiram L. Dadmal ◽  
Dinesh Kumar ◽  
M. Janaki Ramaiah ◽  
Anudeep Kota ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Lung Cancer Cells ◽  
Signalling Pathways ◽  
Lung Cancer Cell ◽  
Cancer Cell Death ◽  
A549 Lung Cancer Cell ◽  
A549 Lung

Fluorinated thiazolidinols cause A549 lung cancer cell death by acting via PI3K/Akt/mTOR and MEK/ERK pathways.

Effect of GPR87 on cell proliferation via KRAS signaling pathway in p53-mutant lung cancer cells.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14713-e14713
Author(s):  
Takayuki Nakano ◽  
Nariyasu Nakashima ◽  
Dage Liu ◽  
Xia Zhang ◽  
Natsumi Matsuura ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cell Viability ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Human Tumor ◽  
Signal Pathway ◽  
Lung Cancer Cells ◽  
Lung Cancer Cell ◽  
P53 Expression

e14713 Background: GPR87 is a member of the cell surface molecular G protein-coupled receptors (GPCRs) family and suggested to contribute to the viability of human tumor cells including lung cancer cell. The mechanism of GPR87 in promote cell proliferation is still not yet well understand. p53 was reported to take an important role in keeping cell viability of GPR87-expressing cells. However, most of lung cancer cells possess p53 mutation. In the present study, several reported signal pathway were investigated in lung cancer cells. Methods: Two p53 mutant GPR87-overexpressing lung cancer cell H358 and PC9 lung cancer cell was investigated. An adenoviral vector that encoded a short hairpin siRNA targeting the GPR87 gene (Ad-shGPR87) was constructed. Real-time RT-PCR was performed to evaluate gene expressions and westen blotting analysis for protein expression. MTT assay was used to evaluate the cell viability. Results: Ad-shGPR87 effectively inhibited the GPR87 expression and significantly reduced the percentage of viable cells in GPR87-overexpression H358 and PC9 cell. Regading the signal pathway, there was no p53 expression in H358 cell and no changes in PC9 cell. However, both cells showed a significant decrease in KRAS and c-Myc gene expression 5 days after Ad-shGPR87 transfection. On the other hand, after Ad-shGPR87 transfection, Akt and Cyclin-D1gene expression decrease slightly in H358, but not in the PC9 cell. Conclusions: Theses result show that GPR87 may promoting cell proliferation through several signaling pathways and that the active in p53 mutant cell may linked to KRAS pathway in lung cancer cell.

scholarly journals USP46 Inhibits Cell Proliferation in Lung Cancer through PHLPP1/AKT Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Wei Wang ◽  
Meng Chen ◽  
Hailing Xu ◽  
Dongqing Lv ◽  
Suna Zhou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Lung Cancer Cells ◽  
Akt Pathway ◽  
Cancer Tissue ◽  
Cancer Cell Proliferation ◽  
Lung Cancer Cell ◽  
Underlying Mechanisms

Previous studies have shown that ubiquitin-specific protease 46 (USP46) is a tumor suppressor in colon cancer and renal cell carcinoma. However, its specific role in other cancers is still poorly understood. This study is aimed at investigating the role of USP46 in lung cancer tumorigenesis and identifying its underlying mechanisms. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting (WB) were used to measure the expression levels of USP46 and PHLPP1 in lung cancer tissue and adjacent normal tissue from patients with lung cancer. We examined the ability of USP46 to regulate cell proliferation in lung cancer cells via cell proliferation assay, radiation assay, genetic overexpression and knockdown, and chemical inhibition of relevant genes. We investigated the underlying mechanisms in multiple lung cancer cell line models by coimmunoprecipitation and ubiquitination assays. In this study, we identified a strong downregulation of the expressions of USP46 and PHLPP1 in lung cancer tissues relative to normal adjacent tissues. USP46 was further shown to inhibit lung cancer cell proliferation under conditions of normal growth and during radiation-induced DNA damage by antagonizing the ubiquitination of PHLPP1 resulting in the inhibition of AKT signaling. Exposure to radiation and AKT inhibition significantly reversed the effect of USP46 siRNA on lung cancer cell proliferation. USP46 is downregulated in lung cancer and suppresses the proliferation of lung cancer cells by inhibiting the PHLPP1/AKT pathway. AKT inhibition slows the proliferation of lung cancer cells that have been downregulated by USP46 and exposed to radiation. This suggests a potential therapeutic avenue for USP46-downregulated lung cancer through a combination of radiation and AKT inhibitor treatment.

Biosynthesized CdS Nanoparticle Induces ROS-dependent Apoptosis in Human Lung Cancer Cells

2021 ◽  
Vol 21 ◽  
Author(s):  
Tina Nasrin ◽  
Mousumi Patra ◽  
Sayed Modinur Rahaman ◽  
Tapan Kumar Das ◽  
Soni Shaikh
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Lung Cancer Cells ◽  
World Health ◽  
Human Lung Cancer ◽  
Ros Production ◽  
Lung Cancer Cell ◽  
Cancer Cell Death

Background: The World Health Organization (WHO) estimated that the number of cancer-related deaths was 9.6 million in 2018 and 2.09 million deaths occurred by lung cancer. The American Institute for Cancer Research (AICR) also observed gender preferences in lung cancer, common in men than women. Since the past decade, nanoparticles have now been widely documented for their anti-cancer properties, which signifies that the development of nanotechnology would be a future diagnosis and treatment strategy for lung cancer. Objective: The current study aimed to investigate the role of biosynthesized CdS nanoparticles (CdS NPs) in lung cancer cells (A549). Therefore, whether the CdS NP induces lung cancer cell death and the underlying mechanism is yet to be elucidated. Methods: Literature was searched from various archives of biomedical and life science journals. Then, CdS NPs were biosynthesized and characterized by traditional and cutting-edge protocols. The CdS NP-mediated cell death was elucidated following standard protocols. Results : CdS NPs induced cytotoxicity towards A549 cells in a dose-dependent manner. However, such a death mechanism does not go through necrosis. Intracellular reactive oxygen species (ROS) accumulation and mitochondrial membrane depolarization demonstrated that cell death is associated with intracellular ROS production. Furthermore, increased sub-G1 population, Bax expression, and decreased Bcl-2 expression revealed that the death was caused by apoptosis. Conclusion: CdS NPs promote apoptosis-mediated lung cancer cell death through ROS production.

Ras association domain family 1C protein stimulates human lung cancer cell proliferation

2006 ◽  
Vol 291 (6) ◽  
pp. L1185-L1190 ◽  
Author(s):  
Yousef G. Amaar ◽  
Marlon G. Minera ◽  
Laurice K. Hatran ◽  
Donna D. Strong ◽  
Subburaman Mohan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Small Interfering Rna ◽  
Lung Cancer Cells ◽  
Cancer Cell Proliferation ◽  
Lung Cancer Cell ◽  
Domain Family ◽  
Interfering Rna

Recently, the Ras association domain family 1 gene ( RASSF1) has been identified as a Ras effector encoding two major mRNA forms, RASSF1A and RASSF1C, derived by alternative promoter selection and alternative mRNA splicing. RASSF1A is a tumor suppressor gene. However, the function of RASSF1C, both in normal and cancer cells, is still unknown. To learn more about the function of RASSF1C in human cancer cells, we tested the effect of silencing RASSF1C mRNA with small interfering RNA on lung cancer cells (NCI H1299) that express RASSF1C but not RASSF1A. Small interfering RNA specific for RASSF1C reduced RASSF1C mRNA levels compared with controls. This reduction in RASSF1C expression caused a significant decrease in lung cancer cell proliferation. Furthermore, overexpression of RASSF1C increased cell proliferation in lung cancer cells. Finally, we found that RASSF1C, unlike RASSF1A, does not upregulate N-cadherin 2 and transglutaminase 2 protein expression in NCI H1299 lung cancer cells. This suggests that RASSF1C and RASSF1A have different effector targets. Together, our findings suggest that RASSF1C, unlike RASSF1A, is not a tumor suppressor but rather stimulates lung cancer cell proliferation.

Exosomal lncRNA FOXD3-AS1 upregulates ELAVL1 expression and activates PI3K/Akt pathway to enhance lung cancer cell proliferation, invasion, and 5-fluorouracil resistance

2021 ◽  
Author(s):  
Guangxian Mao ◽  
Zhimin Mu ◽  
Da Wu
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Rna Binding ◽  
Rna Binding Protein ◽  
A549 Cells ◽  
Akt Pathway ◽  
Lung Cancer Cell

Abstract Long non-coding RNA (lncRNA) FOXD3-AS1 expression is upregulated in lung cancer; however, its effect and mechanism on 5-fluorouracil (5-FU) resistance remain unclear. In this study, we determined the effects of FOXD3-AS1-enriched exosomes derived from lung cancer cells on the proliferation, invasion, and 5-FU resistance of lung cancer cells. Online bioinformatics database analysis showed that FOXD3-AS1 was upregulated in lung cancer progression. Real-time quantitative PCR results confirmed that FOXD3-AS1 expression was upregulated in lung cancer tissues and cell lines, and FOXD3-AS1 was greatly enriched in lung cancer cell-derived exosomes. ELAV-like RNA-binding protein 1 (ELAVL1) was identified as an RNA-binding protein of FOXD3-AS1. The lung cancer cell-derived exosomes promoted A549 cell proliferation and invasion and inhibited apoptosis caused by 5-FU, and transfection of si-FOXD3-AS1 or si-ELAVL1 in exosome-incubated A549 cells reversed these effects. Moreover, exosome-incubated A549 cells were co-transfected with si-FOXD3-AS1 and pcDNA-ELAVL1, showing the same cell proliferation, invasion, and 5-FU resistance as those of A549 cells treated with lung cancer cell-derived exosomes alone. Mechanistic studies identified that lung cancer cell-derived exosomes activated the PI3K/Akt pathway, and transfection of si-FOXD3-AS1 or treatment with the PI3K inhibitor LY294002 reversed the activation of the PI3K/Akt axis induced by exosomes. In conclusion, our study revealed that lung cancer cell-derived exosomal FOXD3-AS1 upregulated ELAVL1 expression and activated the PI3K/Akt pathway to promote lung cancer progression. Our findings provide a new strategy for lung cancer treatment.

scholarly journals MiR-107 inhibits proliferation of lung cancer cells through regulating TP53 regulated inhibitor of apoptosis 1 (TRIAP1)

2017 ◽  
Vol 12 (1) ◽  
pp. 200-205 ◽  
Author(s):  
Bing Wang ◽  
Zhanjie Zuo ◽  
Fang Lv ◽  
Liang Zhao ◽  
Minjun Du ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Western Blot ◽  
Cancer Cells ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Pcr Analysis ◽  
Aberrant Expression ◽  
Small Interference Rna ◽  
Qrt Pcr

AbstractAimsAccumulating evidence indicates that aberrant expression of miR-107 plays a crucial role in cancers. This study aims to display the function of miR-107 and its novel target genes in the progression of lung cancer.Methods and MaterialMiR-107 or miR-107 inhibitor was transfected into lung cancer cells A549. The levels of miR-107 and TP53 regulated inhibition of apoptosis 1 (TRIAP1) were examined by quantitative real-time Polymerase Chain Reaction (qRT-PCR) analysis and Western Blot. Functionally, MTT and colony formation assays were carried out to test the effect of miR-107 inhibitor and/or small interference RNA (siRNA) targeting TRIAP1 mRNA on proliferation of lung cancer cells. Levels of miR-107 or TRIAP1 were detected in clinical lung cancer samples by using qRT-PCR analysis.ResultsQRT-PCR analysis revealed that miR-107 inhibitor or miR-107 was successfully transfected into A549 cells. Western Blot indicated that miR-107 decreased the expression of TRIAP1 protein in the cells. In contrast, miR-107 inhibitor augmented the levels of TRIAP1 protein. Functionally, miR-107 inhibitor remarkably suppressed A549 cell proliferation, whereas, TRIAP1 siRNAs could abrogate the miR-107 inhibitor-induced proliferation of cells. Then, we validated that TRIAP1 was increased in clinical lung cancer samples. MiR-107 expression was negatively related to TRIAP1 expression in clinical lung cancer samples.ConclusionsMiR-107 suppresses cell proliferation by targeting TRIAP1 in lung cancer. Our finding allows new insights into the mechanisms of lung cancer that is mediated by miR-107.

scholarly journals Persistent effects of pair bonding in lung cancer cell growth in monogamous Peromyscus californicus

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Asieh Naderi ◽  
Elham Soltanmaohammadi ◽  
Vimala Kaza ◽  
Shayne Barlow ◽  
Ioulia Chatzistamou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Nude Mice ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Lung Cancer Cell ◽  
Peromyscus Californicus ◽  
Pair Bonds ◽  
The Impact

Epidemiological evidence suggests that social interactions and especially bonding between couples influence tumorigenesis, yet whether this is due to lifestyle changes, homogamy (likelihood of individuals to marry people of similar health), or directly associated with host-induced effects in tumors remains debatable. In the present study, we explored if tumorigenesis is associated with the bonding experience in monogamous rodents at which disruption of pair bonds is linked to anxiety and stress. Comparison of lung cancer cell spheroids that formed in the presence of sera from bonded and bond-disrupted deer mice showed that in monogamous Peromyscus polionotus and Peromyscus californicus, but not in polygamous Peromyscus maniculatus, the disruption of pair bonds altered the size and morphology of spheroids in a manner that is consistent with the acquisition of increased oncogenic potential. In vivo, consecutive transplantation of human lung cancer cells between P. californicus, differing in bonding experiences (n = 9 for bonded and n = 7 for bond-disrupted), and nude mice showed that bonding suppressed tumorigenicity in nude mice (p<0.05), suggesting that the protective effects of pair bonds persisted even after bonding ceased. Unsupervised hierarchical clustering indicated that the transcriptomes of lung cancer cells clustered according to the serum donors’ bonding history while differential gene expression analysis pointed to changes in cell adhesion and migration. The results highlight the pro-oncogenic effects of pair-bond disruption, point to the acquisition of expression signatures in cancer cells that are relevant to the bonding experiences of serum donors, and question the ability of conventional mouse models to capture the whole spectrum of the impact of the host in tumorigenesis.

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