Selective Estrogen Receptor Modulators (SERMs) Synergize with Cisplatin, induce apoptosis and Suppress Cellular Migration and Colony Formation of Lung Cancer Cells

2021 ◽  
Vol 21 ◽  
Author(s):  
Lina Alsous ◽  
Sanaa Bardaweel
Keyword(s):  
Lung Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Colony Formation ◽  
A549 Cells ◽  
Selective Estrogen Receptor Modulators ◽  
Lung Cancer Cells ◽  
Standard Chemotherapy ◽  
Estrogen Receptor Modulators ◽  
Receptor Modulators

Background: Lung cancer remains the leading cause of cancer-related deaths worldwide. Hence, novel therapeutic approaches targeting crucial pathways are needed to improve its treatment. Previous studies have verified the involvement of the estrogen pathway, mediated through estrogen receptor β (ERβ), in the development and progression of lung carcinogenesis. Selective estrogen receptor modulators (SERMs) are a group of estrogen receptor agonists/antagonists that have tissue selective effects. Many of the available SERMs are used for the management of breast cancer. However, their role in lung cancer is still under investigation. Objectives: The aim of this research is to investigate the anti-tumorigenic activity of the selective estrogen receptor modulators, tamoxifen, raloxifene, and toremifene, against different lung cancer cell lines. Methods: The anti-proliferative and combined effects of SERMs with standard chemotherapy were evaluated by MTT assay. Cell migration was assessed using a wound-healing assay. The mechanism of cell death was determined using the Annexin V-FITC/ propidium iodide staining flow cytometry method. Cells’ capability to form colonies was evaluated by soft agar colony formation assay. Estrogen receptors expression was determined using real-time PCR. Results: Our results have demonstrated the presence of ERβ in A549, H1299, and H661 lung cancer cells. Cellular proliferation assay suggested that SERMs have significantly reduced lung cancer cells proliferation in a time and concentration-dependent manner. Additionally, SERMs exhibited a synergistic effect against A549 cells when combined with cisplatin. SERMs treatment have increased cell apoptosis and resulted in concentration-dependent inhibition of cell migration and colony formation of A549 cells. Conclusion: Selective estrogen receptor modulators may possess potential therapeutic utility for the treatment of lung cancer as monotherapy or in combination with standard chemotherapy.

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 Berbamine Inhibits Cell Proliferation and Migration and Induces Cell Death of Lung Cancer Cells via Regulating c-Maf, PI3K/Akt, and MDM2-P53 Pathways

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Lili Liu ◽  
Zhiying Xu ◽  
Binbin Yu ◽  
Li Tao ◽  
Ying Cao
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Colony Formation ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
And Migration ◽  
Proliferation And Migration

Berbamine (BBM) is a natural product isolated from Berberis amurensis Rupr. We investigated the influence of BBM on the cell viability, proliferation, and migration of lung cancer cells and explored the possible mechanisms. The cell viability and proliferation of lung cancer cells were evaluated by MTT assay, EdU assay, and colony formation assay. Migration and invasion abilities of cancer cells were determined through wound scratch assay and Transwell assay. Cell death was evaluated by cell death staining assay and ELISA. The expressions of proteins were evaluated using western blot assay. A xenograft mouse model derived from non-small-cell lung cancer cells was used to detect the effect of BBM on tumor growth and metastasis in vivo. Both colony formation and EdU assays results revealed that BBM (10 μM) significantly inhibited the proliferation of A549 cells ( P < 0.001 ). BBM (10 μM) also significantly inhibited the migration and invasion ability of cancer cells in wound scratch and Transwell assays. Trypan blue assay and ELISA revealed that BBM (20 μM) significantly induced cell death of A549 cells. In xenograft mouse models, the tumor volume was significantly smaller in mice treated with BBM (20 mg/kg). The western blotting assay showed that BBM inhibited the PI3K/Akt and MDM2-p53 signaling pathways, and BBM downregulated the expression of c-Maf. Our results show that BBM inhibits proliferation and metastasis and induces cell death of lung cancer cells in vitro and in vivo. These effects may be achieved by BBM reducing the expression of c-Maf and regulating the PI3K/Akt and MDM2-p53 pathways.

Apelin enhances biological functions in lung cancer A549 cells by downregulating exosomal miR-15a-5p

2020 ◽  
Author(s):  
Jingjing Ran ◽  
Yan Li ◽  
Lei Liu ◽  
Yihan Zhu ◽  
Yinyun Ni ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Colony Formation ◽  
Regulatory Mechanism ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
Cell Group ◽  
Exosomal Mirna ◽  
Proliferation And Invasion

Abstract Apelin acts as a tumor promoter in multiple malignant tumors; however, its regulatory mechanism remains unclear. Previous studies have indicated that exosomes are pivotal to mediating tumor progression and metastasis. This study examined whether apelin enhances proliferation and invasion ability of lung cancer cells via exosomal microRNA (miRNA). Lung cancer A549 cells overexpressing apelin and control vector were generated by lentiviral transfection. Exosomes were isolated from the culture supernatant of each cell group and characterized. A-exo and V-exo were, respectively, cocultured with A549 cells, and assays of proliferation, apoptosis, colony formation and invasion were conducted. Exosomal miRNA sequencing (miRNA-seq) was performed on A-exo and V-exo to select a candidate miRNA. It was found that A549 cells absorbed more A-exo than V-exo, and A-exo could promote proliferation, colony formation, migration and invasion of A549 cells more than V-exo. Exosomal miRNA-seq data revealed that miR-15a-5p was markedly lower in A-exo compared with V-exo. Low expression of miR-15a-5p was also found in lung cancer tissues and cell lines, suggesting that miR-15a-5p may have an anti-tumor role. Overexpression of miR-15a-5p in A549 cells was associated with less cell proliferation, migration, invasion and suppressed cell cycle, and lower amounts of CDCA4 (cell division cycle-associated protein 4) indicated that it may be a potential target for miR-15a-5p. This study elucidated a novel regulatory mechanism that apelin may promote proliferation and invasion of lung cancer cells by inhibiting miR-15a-5p encapsulated in exosomes.

MiRNA-27a sensitizes breast cancer cells to treatment with Selective Estrogen Receptor Modulators

The Breast ◽  
2019 ◽  
Vol 43 ◽  
pp. 31-38 ◽  
Author(s):  
Bojan Ljepoja ◽  
Jonathan García-Roman ◽  
Ann-Katrin Sommer ◽  
Ernst Wagner ◽  
Andreas Roidl
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Selective Estrogen Receptor Modulators ◽  
Estrogen Receptor Modulators ◽  
Receptor Modulators
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