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

Öztürk, Selin Engür; Dikmen, Miriş

doi:10.1007/s11033-022-07329-w

Cited by 5 publications

(12 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After 20 minutes of incubation at room temperature and in the dark, 250 μL of “Annexin V binding buffer” was added to the tubes and apoptotic readings of the groups were performed on the flow cytometry device (Accuri C6, BD Bioscience, New Jersey, ABD) within 30 minutes. [24]…”

Section: Methodsmentioning

confidence: 99%

The investigation of cytotoxic and apoptotic activity of Cl-amidine on the human U-87 MG glioma cell line

Öğüten,

Engür Öztürk,

Dikmen

2024

Medicine

Self Cite

View full text Add to dashboard Cite

Background: Peptidyl (protein) arginine deiminases (PADs) provide the transformation of peptidyl arginine to peptidyl citrulline in the presence of calcium with posttranslational modification. The dysregulated PAD activity plays an important role on too many diseases including also the cancer. In this study, it has been aimed to determine the potential cytotoxic and apoptotic activity of chlorine-amidine (Cl-amidine) which is a PAD inhibitor and whose effectiveness has been shown in vitro and in vivo studies recently on human glioblastoma cell line Uppsala 87 malignant glioma (U-87 MG) forming an in vitro model for the glioblastoma multiforme (GBM) which is the most aggressive and has the highest mortality among the brain tumors. Methods: In the study, the antiproliferative and apoptotic effects of Cl-amidine on GBM cancer model were investigated. The antiproliferative effects of Cl-amidine on U-87 MG cells were determined by 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate method at the 24th and 48th hours. The apoptotic effects were analyzed by Annexin V and Propidium iodide staining, caspase-3 activation, and mitochondrial membrane polarization (5,5’, 6,6’-tetrachloro-1,1’, 3,3’ tetraethyl benzimidazolyl carbocyanine iodide) methods in the flow cytometry. Results: It has been determined that Cl-amidine exhibits notable antiproliferative properties on U-87 MG cell line in a time and concentration-dependent manner, as determined through the 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate assay. Assessment of apoptotic effects via Annexin V and Propidium iodide staining and 5,5’, 6,6’-tetrachloro-1,1’, 3,3’ tetraethyl benzimidazolyl carbocyanine iodide methods has revealed significant efficacy, particularly following a 24-hour exposure period. It has been observed that Cl-amidine induces apoptosis in cells by enhancing mitochondrial depolarization, independently of caspase-3 activation. Furthermore, regarding its impact on healthy cells, it has been demonstrated that Cl-amidine shows lower cytotoxic effects when compared to carmustine, an important therapeutic agent for glioblastoma. Conclusion: The findings of this study have shown that Cl-amidine exhibits significant potential as an anticancer agent in the treatment of GBM. This conclusion is based on its noteworthy antiproliferative and apoptotic effects observed in U-87 MG cells, as well as its reduced cytotoxicity toward healthy cells in comparison to existing treatments. We propose that the antineoplastic properties of Cl-amidine should be further investigated through a broader spectrum of cancer cell types. Moreover, we believe that investigating the synergistic interactions of Cl-amidine with single or combination therapies holds promise for the discovery of novel anticancer agents.

show abstract

Section: Methodsmentioning

confidence: 99%

The investigation of cytotoxic and apoptotic activity of Cl-amidine on the human U-87 MG glioma cell line

Öğüten,

Engür Öztürk,

Dikmen

2024

Medicine

Self Cite

View full text Add to dashboard Cite

show abstract

“…Examining molecular pathways and treatments alongside other cells in the tumor microenvironment is one of the most remarkable problems in cancer research today. Tumor-associated macrophages (TAMS) play a crucial role in the development of cancer progression, angiogenesis, cancer metastasis, and drug resistance [3][4][5][6]. The microenvironment identifies non-cancerous cells and structures within the tumor tissue, and approximately 40% of the mass of solid tumors consists of TAMs [6,7].…”

Section: Introductionmentioning

confidence: 99%

“…M2 macrophages are polarized by different stimuli into alternatively activated macrophage types 2a, 2b, and 2c (M2a, M2b, and M2c). M2 macrophages are polarized into the M2c subtype by interleukin-10 (IL-10), transforming growth factor-beta (TGF-b), and glucocorticoids [3,7]. In a previous study, we used hydrocortisone, a 'well-known glucocorticoid', for the first time in M2c polarization, with a particular emphasis on M2c macrophages [3].…”

Section: Introductionmentioning

confidence: 99%

“…M2 macrophages are polarized into the M2c subtype by interleukin-10 (IL-10), transforming growth factor-beta (TGF-b), and glucocorticoids [3,7]. In a previous study, we used hydrocortisone, a 'well-known glucocorticoid', for the first time in M2c polarization, with a particular emphasis on M2c macrophages [3]. Corticosteroids are synthetic analogues of naturally occurring corticosteroid hormones that are used clinically in many lung-related diseases, such as asthma, pneumonia, and coronavirus disease 2019 (COVID-19) [15].…”

Section: Introductionmentioning

confidence: 99%

“…Bortezomib is the first drug from this group to reach the clinical trial period and be approved by the Food and Drug Administration (FDA). Bortezomib is clinically used in the treatment of multiple myeloma and mantle cell lymphoma [16], and its effects on many solid tumors are still being studied [3,17]. Although bortezomib has been used to treat cancers of hematopoietic origin, such as myeloma, growing basic and clinical studies have also shown that bortezomib is successful in treating many types of solid tumors [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Enhanced angiogenesis of human umbilical vein endothelial cells via THP‐1‐derived M2c‐like macrophages and treatment with proteasome inhibitors ‘bortezomib and ixazomib’

Engür‐Öztürk,

Kaya‐Tİlkİ,

Cantürk

et al. 2024

APMIS

Self Cite

View full text Add to dashboard Cite

The leading cause of cancer‐related death is lung cancer, with metastasis being the most common cause of death. To elucidate the role of macrophages in lung cancer and angiogenesis processes, we established an in vitro co‐culture model of A549 or HUVEC with THP‐1 cells that polarized to M2c macrophages with hydrocortisone. The proteasome inhibitors bortezomib and ixazomib were investigated for their effects on proliferation, invasion, migration, metastasis, and angiogenesis pathways. The effects of bortezomib and ixazomib on gene expression in gene panels, including crucial genes related to angiogenesis and proteasomes, were investigated after the co‐culture model to determine these effects at the molecular level. In conclusion, bortezomib and ixazomib showed antiproliferative effects in both cells, as well as in M2c macrophage co‐culture. M2c macrophages also increased invasion in A549 cells and both invasion and migration in HUVEC. mRNA expression upregulation, specifically in the NFKB and VEGF genes, supported the metastatic and angiogenic effects found in A549 and HUVEC with M2c macrophage co‐culture. Additionally, bortezomib inhibited the VEGFB pathway in HUVEC and NFKB1 in A549 cells. The significant findings obtained as a result of this study will provide information regarding angiogenesis induced by M2 macrophages.

show abstract

Proteasome inhibitors reduce CD73 expression partly via decreasing p-ERK in NSCLC cells

Su,

Tian,

et al. 2023

Life Sciences

View full text Add to dashboard Cite

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

Cited by 5 publications

References 47 publications

The investigation of cytotoxic and apoptotic activity of Cl-amidine on the human U-87 MG glioma cell line

The investigation of cytotoxic and apoptotic activity of Cl-amidine on the human U-87 MG glioma cell line

Enhanced angiogenesis of human umbilical vein endothelial cells via THP‐1‐derived M2c‐like macrophages and treatment with proteasome inhibitors ‘bortezomib and ixazomib’

Proteasome inhibitors reduce CD73 expression partly via decreasing p-ERK in NSCLC cells

Contact Info

Product

Resources

About