scholarly journals Repeated Irradiation with γ-Ray Induces Cancer Stemness through TGF-β-DLX2 Signaling in the A549 Human Lung Cancer Cell Line

2021 ◽  
Vol 22 (8) ◽  
pp. 4284
Author(s):  
Hae-Ran Park ◽  
Yeo-Jin Choi ◽  
Jee-Young Kim ◽  
In-Gyu Kim ◽  
Uhee Jung
Keyword(s):  
Molecular Markers ◽  
Cancer Cells ◽  
A549 Cells ◽  
Lung Cancer Cell Line ◽  
Human Lung Cancer ◽  
Migration And Invasion ◽  
Stem Cell Markers ◽  
Fractionated Irradiation ◽  
Cancer Stemness ◽  
Cancer Stem Cell Markers

Cancer stem cells (CSCs) play an important role in cancer recurrence and metastasis. It is suggested that the CSC properties in heterogeneous cancer cells can be induced by ionizing radiation (IR). This study investigated the role of DLX2 in the radioresistance and CSC properties induced by IR in NSCLC cancer cells. Here, A549 cells were exposed to fractionated irradiation at a cumulative dose of 52 Gy (4 Gy × 13 times) for a generation of radioresistant cells. After fractionated irradiation, surviving A549 cells exhibited resistance to IR and enhanced expression of various cancer stem cell markers. They also showed upregulation of mesenchymal molecular markers and downregulation of epithelial molecular markers, correlating with an increase in the migration and invasion. Fractionated irradiation triggered the secretion of TGF-β1 and DLX2 expression. Interestingly, the increased DLX2 following fractionated irradiation seemed to induce the expression of the gene for the EGFR-ligand betacellulin via Smad2/3 signaling. To contrast, DLX2 knockdown dramatically decreased the expression of CSC markers, migration, and proliferation. Moreover, A549 cells expressing DLX2 shRNA formed tumors with a significantly smaller volume compared to those expressing control shDNA in a mouse xenograft assay. These results suggest that DLX2 overexpression in surviving NSCLC cancer cells after fractionated IR exposure is involved in the cancer stemness, radioresistance, EMT, tumor survival, and tumorigenic capability.

scholarly journals Combination of Sasa quelpaertensis Nakai Leaf Extract and Cisplatin Suppresses the Cancer Stemness and Invasion of Human Lung Cancer Cells

2014 ◽  
Vol 13 (6) ◽  
pp. 529-540 ◽  
Author(s):  
Mina Kim ◽  
Yoo-Sun Kim ◽  
Kyung-Mi Kim ◽  
Hee-Chul Ko ◽  
Se-Jae Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Human Lung ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Stem Cell Markers ◽  
Cancer Stemness ◽  
Human Lung Cancer Cells

Lung cancer is the leading cause of cancer death worldwide, and most chemotherapeutic drugs have limited success in treating this disease. Furthermore, some drugs show undesirable side effects due to the enrichment of cancer stem cells (CSCs) that are present, leading to resistance to conventional chemotherapy and tumor relapse. CSCs possess self-renewal characteristics, aggressive tumor initiating activity, and ability to facilitate tumor metastasis. Therefore, development of nontoxic agents that can potentiate chemotherapy and eliminate CSCs would be highly desirable. In the present study, we investigated whether Sasa quelpaertensis leaf extracts (SQE) and cisplatin (CIS), individually or in combination, would exert anti-CSC and antimetastatic effect in H1299 and A549 human lung cancer cells. Following these treatments, cell growth, phosphorylation of phosphoinositide-3 kinase, and activation of the mammalian target of rapamycin were inhibited. Decreased serial sphere formation, clonogenicity, and expression of major stem cell markers, such as CD44 and SOX-2, in CD44+ cancer stem cells were also observed. In addition, inhibition of cell migration and invasion in both cell lines as well as inhibition of matrix metalloproteinase-2 activity and expression were detected. Importantly, the anticancer stemness and antimetastasis effects in each of these assays were greater for the combined treatment with SQE and CIS than with each treatment individually. In conclusion, the data suggest that SQE alone, or in combination with CIS, represents a promising therapeutic strategy for eliminating cancer stemness and cell invasion potential of CSCs, thereby treating and preventing metastatic lung cancer cells.

scholarly journals Terrein Inhibits Aggressive Phenotype of A549 Human Lung Cancer Cell through Suppression of HIF-1α

2021 ◽  
Vol 18 (11) ◽  
Author(s):  
Paiwan BUACHAN ◽  
Maneekarn NAMSA-AID ◽  
Wanlaya TANECHPONGTAMB
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
A549 Cells ◽  
Specific Effect ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Migration And Invasion ◽  
Normal Cells ◽  
Aggressive Phenotype

Terrein is a fungal metabolite that has already been reported with anticancer properties. However, the effect on the aggressive phenotype of cancer cells has not been elucidated yet.  In the present study, the cytotoxicity of terrein was first determined against lung cancer cells (A549) model and compared with several normal cell lines (Vero, L6, and H9C2 cells). The data demonstrated that terrein had a specific effect on A549 cells relative to normal cells with high selectivity index values. Then, the hypoxic model that recognized to induce aggressive abilities was established in A549 cells by cobalt chloride (CoCl2) stimulation. With this model, terrein could reduce HIF-1α, a marker of hypoxia, and inhibit both migration and invasion of which the effect on invasion is more explicit. Our results demonstrated that terrein has a potential new role as the anti-aggressive phenotype by inhibiting cancer cell migration and invasion through HIF-1α reduction. HIGHLIGHTS Terrein, a secondary bioactive metabolite extracted from Aspergillus terreus, demonstrates anticancer effect on lung cancer cells with less cytotoxic on normal cells CoCl2 treatment was successfully used for creating hypoxic model which resulting in HIF-1a augmentation and aggressive abilities enhancement in lung cancer cells Terrein could reduce HIF-1a expression and invasive ability of lung cancer cells demonstrated the potential role as anti-metastatic agent for lung cancer GRAPHICAL ABSTRACT

scholarly journals miR-34a-5p might have an important role for inducing apoptosis by down-regulation of SNAI1 in apigenin-treated lung cancer cells

2021 ◽  
Author(s):  
Rieko Aida ◽  
Keitaro Hagiwara ◽  
Kazunori Okano ◽  
Kyoko Nakata ◽  
Yuho Obata ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Microarray Analysis ◽  
A549 Cells ◽  
Polymerase Chain Reaction Analysis ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Migration And Invasion ◽  
Microrna Target ◽  
Down Regulation

AbstractApigenin is a flavonoid with antioxidant and anticancer effects. It has been reported that apigenin inhibits proliferation, migration, and invasion and induces apoptosis in cultured lung cancer cells. However, there is little information on the involvement of microRNAs (miRNAs) in its effects. miRNA microarray analysis and polymerase-chain-reaction analysis of miRNAs revealed that treatment of human lung cancer A549 cells with apigenin up-regulated the level of miR-34a-5p. Furthermore, mRNA microarray analysis and the results of three microRNA target prediction tools showed that Snail Family Transcriptional Repressor 1 (SNAI1), which inhibits the induction of apoptosis, had its mRNA expression down-regulated in A549 cells treated with apigenin. Our findings suggest that apigenin might induce apoptosis by down-regulation of SNAI1 through up-regulation of miR-34a-5p in A549 cells.

scholarly journals Synthesis and Encapsulation of a New Zinc Phthalocyanine Photosensitizer into Polymeric Nanoparticles to Enhance Cell Uptake and Phototoxicity

2019 ◽  
Vol 9 (3) ◽  
pp. 401 ◽  
Author(s):  
Nahid Mehraban ◽  
Phillip Musich ◽  
Harold Freeman
Keyword(s):  
Photodynamic Therapy ◽  
Cancer Cells ◽  
Parent Compound ◽  
A549 Cells ◽  
Cancer Cell Line ◽  
Lung Cancer Cell Line ◽  
Cell Uptake ◽  
Zinc Phthalocyanine ◽  
Human Lung Cancer ◽  
Surrounding Tissue

Efforts to enhance the utility of photodynamic therapy as a non-invasive method for treating certain cancers have often involved the design of dye sensitizers with increased singlet oxygen efficiency. More recently, however, sensitizers with greater selectivity for tumor cells than surrounding tissue have been targeted. The present study provides an approach to the modification of the known photosensitizer zinc phthalocyanine (ZnPc), to enhance its solubility and delivery to cancer cells. Targeting a photosensitizer to the site of action improves the efficacy of the sensitizer in photodynamic therapy. In this work we used PLGA-b-PEG to encapsulate a new zinc phthalocyanine derivative, 2(3), 9(10), 16(17), 23(24)-tetrakis-(4’-methyl-benzyloxy) phthalocyanine zinc(II) (ZnPcBCH3), to enhance uptake into A549 cells, a human lung cancer cell line. ZnPcBCH3 exhibited the same photochemical properties as the parent compound ZnPc but gave increased solubility in organic solvents, which allowed for efficient encapsulation. In addition, the encapsulated dye showed a near 500-fold increase in phototoxicity for A549 cancer cells compared to free dye.

Cochinchina MomordicaSeed Suppresses Proliferation and Metastasis in Human Lung Cancer Cells by Regulating Multiple Molecular Targets

2015 ◽  
Vol 43 (01) ◽  
pp. 149-166 ◽  
Author(s):  
Yang Shen ◽  
Linyi Meng ◽  
Huajun Sun ◽  
Yizhun Zhu ◽  
Hongrui Liu
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Human Lung ◽  
A549 Cells ◽  
Molecular Targets ◽  
Human Lung Cancer ◽  
Migration And Invasion ◽  
Human Lung Cancer Cells ◽  
Proliferation And Metastasis ◽  
Specific Inhibitors

Cochinchina Momordica Seed, which is the dried ripe seed of Momordica cochinchinensis (Lour.) Spreng, has been used as a mainly anticancer ingredient for many years in China. This study aims at investigating the roles of an ethanol-soluble extract of Cochinchina Momordica Seed (ECMS) in suppressing the proliferation and metastasis of human lung cancer cells, and further elucidating underlying molecular mechanisms. Our researches suggest that ECMS dose-dependently decreased the survival rates of A549 and H1299 cells, and inhibited the migration and invasion in A549 cells. ECMS-induced apoptosis was accompanied by up-regulation of p53, Bax and the down-regulation of Bcl-2, PI-3K/Akt signal pathway, and resulted in the dissipation of mitochondrial membrane potential (ΔΨm) and sequentially activated caspase-3 cascade. Pre-treated with specific inhibitors, LY294002 (PI-3K inhibitor) and BAY11-7082 (NF-κB inhibitor) could enhance the anti-proliferation effects of ECMS on A549 cells. Furthermore, ECMS could increase the level of E-cadherin and decrease of the level of STAT-3 and MMP-2, and scarcely affected the expression of VEGF, and resulted in the inhibition of migration and invasion. Pre-treated with specific inhibitors, WP1066 (STAT-3 inhibitor) and TIMP-2 (MMP-2 inhibitor) could enhance the inhibitory effects of ECMS on migration. In conclusion, the current data demonstrated ECMS inhibited the proliferation of A549 cells by inducing apoptosis, at least partly through the activation of p53 and inactivation of PI-3K/Akt signaling. STAT-3 and MMP-2 pathways may be partly involved in anti-metastasis activities of ECMS. Hence, ECMS might be a promising candidate for the therapy of the non-small cell lung cancer by regulating multiple molecular targets.

scholarly journals Ovalitenone Inhibits the Migration of Lung Cancer Cells via the Suppression of AKT/mTOR and Epithelial-to-Mesenchymal Transition

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 638
Author(s):  
Kittipong Sanookpan ◽  
Nongyao Nonpanya ◽  
Boonchoo Sritularak ◽  
Pithi Chanvorachote
Keyword(s):  
Lung Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Colony Formation ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
Mesenchymal Transition

Cancer metastasis is the major cause of about 90% of cancer deaths. As epithelial-to-mesenchymal transition (EMT) is known for potentiating metastasis, this study aimed to elucidate the effect of ovalitenone on the suppression of EMT and metastasis-related behaviors, including cell movement and growth under detached conditions, and cancer stem cells (CSCs), of lung cancer cells. Methods: Cell viability and cell proliferation were determined by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazo-liumbromide (MTT) and colony formation assays. Cell migration and invasion were analyzed using a wound-healing assay and Boyden chamber assay, respectively. Anchorage-independent cell growth was determined. Cell protrusions (filopodia) were detected by phalloidin-rhodamine staining. Cancer stem cell phenotypes were assessed by spheroid formation. The proteins involved in cell migration and EMT were evaluated by Western blot analysis and immunofluorescence staining. Results: Ovalitenone was used at concentrations of 0–200 μM. While it caused no cytotoxic effects on lung cancer H460 and A549 cells, ovalitenone significantly suppressed anchorage-independent growth, CSC-like phenotypes, colony formation, and the ability of the cancer to migrate and invade cells. The anti-migration activity was confirmed by the reduction of filopodia in the cells treated with ovalitenone. Interestingly, we found that ovalitenone could significantly decrease the levels of N-cadherin, snail, and slug, while it increased E-cadherin, indicating EMT suppression. Additionally, the regulatory signaling of focal adhesion kinase (FAK), ATP-dependent tyrosine kinase (AKT), the mammalian target of rapamycin (mTOR), and cell division cycle 42 (Cdc42) was suppressed by ovalitenone. Conclusions: The results suggest that ovalitenone suppresses EMT via suppression of the AKT/mTOR signaling pathway. In addition, ovalitenone exhibited potential for the suppression of CSC phenotypes. These data reveal the anti-metastasis potential of the compound and support the development of ovalitenone treatment for lung cancer therapy.

Synthesis and in vitro cytotoxicity evaluation of ruthenium polypyridyl-sensitized paramagnetic titania nanoparticles for photodynamic therapy

RSC Advances ◽  
2016 ◽  
Vol 6 (53) ◽  
pp. 47520-47529 ◽  
Author(s):  
Mohammad H. Sakr ◽  
Najeeb M. Halabi ◽  
Leen N. Kalash ◽  
Sara I. Al-Ghadban ◽  
Mayyasa K. Rammah ◽  
...  
Keyword(s):  
A549 Cells ◽  
Cancer Cell Line ◽  
In Vitro Cytotoxicity ◽  
Lung Cancer Cell Line ◽  
Titania Nanoparticles ◽  
Human Lung Cancer ◽  
Type I ◽  
Dye Sensitized ◽  
Photo Dynamic Therapy

We demonstrate the effective cytotoxic properties of a dye-sensitized metal oxide in an in vitro model of a human lung cancer cell line (A549 cells) upon light irradiation, where a type I mechanism photo-dynamic therapy is realized exclusively.

scholarly journals Propofol Inhibits Lung Cancer A549 Cell Growth and Epithelial‐Mesenchymal Transition Process by Upregulation of MicroRNA-1284

2018 ◽  
Vol 27 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Wei-Zhen Liu ◽  
Nian Liu
Keyword(s):  
Lung Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
A549 Cell ◽  
Epithelial Mesenchymal Transition ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Foxm1 Expression

Propofol has been widely used in lung cancer resections. Some studies have demonstrated that the effects of propofol might be mediated by microRNAs (miRNAs). This study aimed to investigate the effects and mechanisms of propofol on lung cancer cells by regulation of miR-1284. A549 cells were treated with different concentrations of propofol, while transfected with miR-1284 inhibitor, si-FOXM1, and their negative controls. Cell viability, migration, and invasion, and the expression of miR-1284, FOXM1, and epithelial‐mesenchymal transition (EMT) factors were detected by CCK-8, Transwell, qRT-PCR, and Western blot assays, respectively. In addition, the regulatory and binding relationships among propofol, miR-1284, and FOXM1 were assessed, respectively. Results showed that propofol suppressed A549 cell viability, migration, and invasion, upregulated E-cadherin, and downregulated N-cadherin, vimentin, and Snail expressions. Moreover, propofol significantly promoted the expression of miR-1284. miR-1284 suppression abolished propofol-induced decreases of cell viability, migration, and invasion, and increased FOXM1 expression and the luciferase activity of FOXM1-wt. Further, miR-1284 negatively regulated FOXM1 expression. FOXM1 knockdown reduced cell viability, migration, and invasion by propofol treatment plus miR-1284 suppression. In conclusion, our study indicated that propofol could inhibit cell viability, migration, invasion, and the EMT process in lung cancer cells by regulation of miR-1284.

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