scholarly journals Proteasome Inhibitor Immunotherapy for the Epithelial to Mesenchymal Transition: Assessing the A549 Lung Cancer Cell Microenvironment and the Role of M1, M2a and M2c ‘Hydrocortisone-Polarised’ Macrophages

2022 ◽  
Author(s):  
Selin Engür Öztürk ◽  
Miriş DİKMEN
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
A549 Cell ◽  
Epithelial To Mesenchymal Transition ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Mesenchymal Transition ◽  
Cell Microenvironment ◽  
A549 Lung

Abstract Lung cancer is a leading cause of cancer-related deaths, primarily as a result of metastases. In this metastasis, the epithelial-to-mesenchymal transition (EMT) is essential. Interaction with the cancer cell microenvironment is primarily dependent on M1- and M2-polarized macrophage. In this study, we revealed the EMT-associated activity of M1, M2a and M2c macrophages in A549 lung cancer cells. We established a co-culture model of A549 lung cancer cells utilizing THP-1-derived M1/M2 polarised macrophages to explore the involvement of macrophages in the immune response, apoptosis, and EMT in lung cancer. Although multiple polarising agents are routinely used for M1 and M2 conversion, we assessed a new possible polarising agent, hydrocortisone. M1 increased A549 cell sensitivity to proteasome inhibitors and decreased A549 cell viability by inducing apoptosis. EMT was induced in the presence of M2c macrophages in A549 cells by the levels of vimentin, fibronectin, E-cadherin, NF-kB, CCL-17. We also revealed the antiproliferative effects of bortezomib and ixazomib on A549 cells in both 2D and 3D cultures. Our findings could help develop an immunotherapeutic strategy by shedding light on a previously undiscovered part of the EMT pathway. Furthermore, additional investigation may reveal that polarising tumour-associated macrophages to M1 and eliminating the M2a or particularly the M2c subtype are effective anti-cancer strategies.

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.

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.

scholarly journals miR-149 Inhibits Non-Small-Cell Lung Cancer Cells EMT by Targeting FOXM1

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Yang Ke ◽  
Weiyong Zhao ◽  
Jie Xiong ◽  
Rubo Cao
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Lung Cancer ◽  
Epithelial To Mesenchymal Transition ◽  
A549 Cells ◽  
Small Cell ◽  
Lung Cancer Cells ◽  
Small Cell Lung ◽  
Mesenchymal Transition

MicroRNAs (miRNAs) have been implied to play crucial roles for epithelial-to-mesenchymal transition (EMT) of non-small-cell lung cancer cells (NSCLC cells). Here we found that the expression of miR-149, downregulated in lung cancer, was inversely correlated with invasive capability and the EMT phenotype of NSCLC cells. miR-149 inhibited EMT in NSCLC cells. Furthermore, we demonstrated that miR-149 directly targeted Forkhead box M1 (FOXM1), and FOXM1 was involved in the EMT induced by TGF-β1 in A549 cells. Overexpression of FOXM1 restored EMT process inhibited by miR-149. Our work suggested that miR-149 might be an EMT suppressor in NSCLC cells.

scholarly journals Epithelial-to-mesenchymal transition of A549 lung cancer cells exposed to electronic cigarettes

Lung Cancer ◽  
2018 ◽  
Vol 122 ◽  
pp. 224-233 ◽  
Author(s):  
Atena Zahedi ◽  
Rattapol Phandthong ◽  
Angela Chaili ◽  
Guadalupe Remark ◽  
Prue Talbot
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Electronic Cigarettes ◽  
Lung Cancer Cells ◽  
Mesenchymal Transition ◽  
A549 Lung

scholarly journals Antitumoral effects of Santolina chameacyparissus on Non-Small Cell Lung Cancer Cells

2021 ◽  
Vol 38 (3) ◽  
pp. 294-300
Author(s):  
Yasemin SAYGIDEGER ◽  
Burcu SAYGIDEGER DEMIR ◽  
Tugba TASKIN TOK ◽  
Alper AVCI ◽  
Aycan SEZAN ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Lung Cancer ◽  
Epithelial To Mesenchymal Transition ◽  
A549 Cells ◽  
Small Cell ◽  
Lung Cancer Cells ◽  
Small Cell Lung ◽  
Mesenchymal Transition

Santolina chameacyparissus (Santo) is an evergreen plant which is traditionally used for its anti-inflammatory effects in various diseases. In this study, we aimed to explore the effects of Santo in non-small cell lung cancer cells. We extracted volatile oil from the plant and evaluated cytotoxicity, apoptosis, and motility effects of the extract on two non-small cell lung cancer (NSCLC) cell lines; one is a patient derived and the other one is a commercially available A549 cells. We also identified its components via GC/MS and investigated possible targets of the major components of the plant using qPCR and docking studies. Cytotoxicity tests showed dose dependent cell killing activity and flow cytometry assays exposed apoptotic effects of Santo. The essential oil also remarkably decreased migration rate of A549 cells, therefore we evaluated the expression levels of epithelial to mesenchymal transition related genes E-cadherin and Vimentin ratio, ZEB1 and SNAIL and another motility related gene Ezrin. Santo did not change the expression of EMT related genes but decreased Ezrin levels. According to the results of the GS/MS analysis, Artemisia ketone and Camphor were identified as major molecules of the extract. Docking analysis also revealed that artemisia ketone, the major component of the Santo extract, potentially showed strong binding to the active site of ezrin protein and both artemisia ketone and camphor had ability to bind DNA. The results of the present study indicate that Santo and its components artemisia ketone and camphor are promising anti-cancer agents, and their potential in targeting DNA and oncogenic proteins in the lung cancer cells seems worth to focus on this plant in cancer related drug discovery science.

scholarly journals IL-37 Confers Anti-Tumor Activity by Regulation of m6A Methylation

2021 ◽  
Vol 10 ◽  
Author(s):  
Xiaofeng Mu ◽  
Qi Zhao ◽  
Wen Chen ◽  
Yuxiang Zhao ◽  
Qing Yan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
A549 Cells ◽  
Protective Role ◽  
Lung Cancer Cells ◽  
Rna Seq ◽  
Mesenchymal Transition ◽  
Cancer Tissues ◽  
Anti Tumor Activity

N6-methyladenosine (m6A) is a common transcriptomic modification in cancer. Recently, it has been found to be involved in the regulation of non-small cell lung cancer (NSCLC) formation and metastasis. Interleukin 37 (IL-37) plays a crucial protective role in lung cancer. In our previous studies, we found that IL-37 is a potential novel tumor suppressor by inhibiting IL-6 expression to suppress STAT3 activation and decreasing epithelial-to-mesenchymal transition. Moreover, we found that treatment of IL-37 in lung cancer cells induced widespread and dynamic RNA m6A methylation. The effects of RNA m6A methylation of IL-37 treatment require further study. However, the functions of RNA m6A methylation of IL-37 treatment still await elucidation. Using MeRIP-seq and RNA-seq, we uncovered a unique m6A methylation profile in the treatment of IL-37 on the A549 cell line. We also showed the expression of m6A writers METTL3, METTL14, and WTAP and erasers ALKBH5 and FTO in A549 cells and lung cancer tissues after the treatment of IL-37. This study showed that IL-37 could lead to changes in m6A methylation level and related molecule expression level in A546 cells and may downregulate the proliferation by inhibiting Wnt5a/5b pathway in A549 cells. We conclude that IL-37 suppresses tumor growth through regulation of RNA m6A methylation in lung cancer cells.

scholarly journals Isorhamnetin inhibited migration and invasion via suppression of Akt/ERK-mediated epithelial-to-mesenchymal transition (EMT) in A549 human non-small-cell lung cancer cells

2019 ◽  
Vol 39 (9) ◽  
Author(s):  
Wei Luo ◽  
Qingbin Liu ◽  
Nan Jiang ◽  
Mingquan Li ◽  
Li Shi
Keyword(s):  
Lung Cancer ◽  
Cell Adhesion ◽  
Protein Expression ◽  
Cancer Cells ◽  
A549 Cell ◽  
Epithelial To Mesenchymal Transition ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Migration And Invasion ◽  
Mesenchymal Transition

Abstract In the present study, we investigated the potential effects of Isorhamnetin on the growth and metastasis of A549 human lung cancer cells, as well as the underlying mechanism. Treatment with Isorhamnetin exhibited a dose- and time-dependent inhibition on A549 cell proliferation. Furthermore, the cell adhesion and Transwell assay showed that treatment with Isorhamnetin (2.5, 5, and 10 μM) for 48 h resulted in a significant inhibition effect on cell adhesion, invasion and migration of A549 cells, depending on concentration, which was associated with the suppression of matrix metalloproteinase (MMP)-2 and MMP-9 activity and protein expression. Moreover, Isorhamnetin effectively suppressed the expressions of epithelial-to-mesenchymal transition (EMT) markers, as evidenced by the down-regulation of N-cadherin, vimentin and snail, as well as up-regulation of E-cadherin protein expression. Additionally, these inhibitions were mediated by interrupting AKT/ERK1/2 signaling pathways. Taken together, the results of the current study demonstrated that Isorhamnetin may become a good anti-metastastic agent against lung cancer A549 cell line by the suppression of EMT via interrupting Akt/ERK1/2 signaling pathway.

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