scholarly journals Pentagalloyl glucose inhibits TNF‐α‐activated CXCL1/GRO-α expression and induces apoptosis‐related genes in triple-negative breast cancer cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Patricia Mendonca ◽  
Sumaih Alghamdi ◽  
Samia Messeha ◽  
Karam F. A. Soliman
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Cancer Progression ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Fold Increase ◽  
Mapk Signaling ◽  
Tnf Α ◽  
Pentagalloyl Glucose

AbstractIn triple-negative breast cancer (TNBC), the tumor microenvironment is associated with increased proliferation, suppressing apoptotic mechanisms, an altered immune response, and drug resistance. The current investigation was designed to examine the natural compound pentagalloyl glucose (PGG) effects on TNF-α activated TNBC cell lines, MDA-MB-231 and MDA-MB-468. The results obtained showed that PGG reduced the expression of the cytokine GRO-α/CXCL1. PGG also inhibited IƙBKE and MAPK1 genes and the protein expression of IƙBKE and MAPK, indicating that GRO-α downregulation is possibly through NFƙB and MAPK signaling pathway. PGG also inhibited cell proliferation in both cell lines. Moreover, PGG induced apoptosis, modulating caspases, and TNF superfamily receptor genes. It also augmented mRNA of receptors DR4 and DR5 expression, which binds to TNF-related apoptosis-induced ligand, a potent and specific stimulator of apoptosis in tumors. Remarkably, PGG induced a 154-fold increase in TNF expression in MDA-MB-468 compared to a 14.6-fold increase in MDA-MB-231 cells. These findings indicate PGG anti-cancer ability in inhibiting tumor cell proliferation and GRO-α release and inducing apoptosis by increasing TNF and TNF family receptors' expression. Thus, PGG use may be recommended as an adjunct therapy for TNBC to increase chemotherapy effectiveness and prevent cancer progression.

scholarly journals Overexpression of SERPINA3 promotes tumor invasion and migration, epithelial-mesenchymal-transition in triple-negative breast cancer cells

Breast Cancer ◽  
2021 ◽  
Author(s):  
Yingzi Zhang ◽  
Jiao Tian ◽  
Chi Qu ◽  
Yang Peng ◽  
Jinwei Lei ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Epithelial Mesenchymal Transition ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Tnbc Cell

Abstract Background Recent studies have indicated that serpin peptidase inhibitor, clade A, member 3 (SERPINA3) is a potential marker associated with tumor progression, which connoted that SERPINA3 is related to malignant phenotypes in cancer. However, the biological function of SERPINA3 in breast cancer (BC) remains unclear. Methods Bioinformatics data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Immunohistochemical staining (IHC) was conducted to determine SERPINA3 expression. With strong aggressive abilities, triple-negative breast cancer (TNBC) cell lines (MDA-MB-231, BT549 and MDA-MB-436) were obtained to examine SERPINA3 expression and functions. Wound healing and Transwell assays were performed to measure cell migration and invasion. Cell Counting Kit-8 (CCK-8) assay was conducted to detect cell proliferation abilities and cell viabilities. Results SERPINA3 was upregulated in BC tissues. Functional assays suggested that overexpression of SERPINA3 significantly promoted cell proliferation, where migration and invasion of TNBC cells were accelerated. Knockdown of SERPINA3 had the opposite effects. These results causing by overexpression of SERPINA3 were also confirmed in non-TNBC cell lines. Overexpression of SERPINA3 remarkably enhanced the epithelial–mesenchymal transition (EMT) by upregulating the EMT markers and EZH2. In addition, the overexpression of SERPINA3 reduced the sensitivity of TNBC cells to cisplatin. Conclusion SERPINA3 can regulate the migration, invasion and EMT of TNBC cells and increased expression of SERPINA3 confers resistance to cisplatin in TNBC cells. We discern it is required for the regulation of BC progression and is a critical target for the clinical treatment of BC.

scholarly journals Integrative analysis of mRNA and miRNA profiles identifies miR-193 and miR-210 as potential regulatory biomarkers in different molecular subtypes of breast cancer

2020 ◽  
Author(s):  
Adriane Feijo Evangelista ◽  
Renato J Oliveira ◽  
Viviane A O Silva ◽  
Rene A D C Vieira ◽  
Rui M Reis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Line ◽  
Cell Lines ◽  
Breast Cancer Cell ◽  
Cancer Progression ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
Breast Cancer Cell Lines ◽  
Mcf 7

Abstract Introduction: Breast cancer is the most frequently diagnosed malignancy among women. However, the role of microRNA expression in breast cancer progression is not fully understood. In this study we examined predictive interactions between differentially expressed miRNAs and mRNAs in breast cancer cell lines representative of the common molecular subtypes. Integrative bioinformatics analysis identified miR-193 and miR-210 as potential regulatory biomarkers of mRNA in breast cancer. Several recent studies have investigated these miRNAs in a broad range of tumors, but the mechanism of their involvement in cancer progression has not previously been investigated. Methods: The miRNA-mRNA interactions in breast cancer cell lines were identified by parallel expression analysis and miRNA target prediction programs. The expression profiles of mRNA and miRNAs from luminal (MCF-7, MCF-7/AZ and T47D), HER2 (BT20 and SK-BR3) and triple negative subtypes (Hs578T e MDA-MB-231) could be clearly separated by unsupervised analysis using HB4A cell line as a control. Breast cancer miRNA data from TCGA patients were grouped according to molecular subtypes and then used to validate these findings. Expression of miR-193 and miR-210 was investigated by miRNA transient silencing assays using the MCF7, BT20 and MDA-MB-231 cell lines. Functional studies included, xCELLigence system, ApoTox-Glo triplex, flow cytometry and transwell assays were performed to determine cell proliferation, cytotoxicity, apoptosis, migration and invasion, respectively. Results: The most evident effects were associated with cell proliferation after miR-210 silencing in triple negative subtype cell line MDA-MB-231. Using in silico prediction algorithms, TNFRSF10 was identified as one of the potential downstream targets for both miRNAs. The TNFRSF10C and TNFRSF10D mRNA expression inversely correlated with the expression levels of miR-193 and miR210 in breast cell lines and breast cancer patients, respectively. Other potential regulated genes whose expression also inversely correlated with both miRNAs were CCND1, a mediator on invasion and metastasis, and the tumor suppressor gene RUNX3. Conclusion: In summary, our findings identify miR-193 and miR-210 as potential regulatory miRNA in different molecular subtypes of breast cancer and suggest that miR-210 may have specific role in MDA-MB-231 proliferation. Our results highlight important new downstream regulated targets that may serve as promising therapeutic pathways for aggressive breast cancers.

scholarly journals The inhibitory effects of butein on cell proliferation and TNF-α-induced CCL2 release in racially different triple negative breast cancer cells

PLoS ONE ◽  
2019 ◽  
Vol 14 (10) ◽  
pp. e0215269
Author(s):  
Patricia Mendonca ◽  
Ainsley Horton ◽  
David Bauer ◽  
Samia Messeha ◽  
Karam F. A. Soliman
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Inhibitory Effects ◽  
Tnf Α

scholarly journals KDM4C Activity Modulates Cell Proliferation and Chromosome Segregation in Triple-Negative Breast Cancer

2016 ◽  
Vol 10 ◽  
pp. BCBCR.S40182 ◽  
Author(s):  
Jeison Garcia ◽  
Fernando Lizcano
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Progression ◽  
Chromosome Segregation ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Human Cancer ◽  
Histone Demethylase ◽  
Breast Cancer Cell Lines ◽  
Demethylase Activity

The Jumonji-containing domain protein, KDM4C, is a histone demethylase associated with the development of several forms of human cancer. However, its specific function in the viability of tumoral lineages is yet to be determined. This work investigates the importance of KDM4C activity in cell proliferation and chromosome segregation of three triple-negative breast cancer cell lines using a specific demethylase inhibitor. Immunofluorescence assays show that KDM4C is recruited to mitotic chromosomes and that the modulation of its activity increases the number of mitotic segregation errors. However, 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) cell proliferation assays demonstrate that the demethylase activity is required for cell viability. These results suggest that the histone demethylase activity of KDM4C is essential for breast cancer progression given its role in the maintenance of chromosomal stability and cell growth, thus highlighting it as a potential therapeutic target.

scholarly journals Lamin B2 promotes the progression of triple negative breast cancer via mediating cell proliferation and apoptosis

2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Cui-Cui Zhao ◽  
Jing Chen ◽  
Li-Ying Zhang ◽  
Hong Liu ◽  
Chuan-Gui Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Progression ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
The Cancer Genome Atlas ◽  
Proliferation And Apoptosis

Abstract Triple negative breast cancer (TNBC) is a more common type of breast cancer with high distant metastasis and poor prognosis. The potential role of lamins in cancer progression has been widely revealed. However, the function of lamin B2 (LMNB2) in TNBC progression is still unclear. The present study aimed to investigate the role of LMNB2 in TNBC. The cancer genome atlas (TCGA) database analysis and immunohistochemistry (IHC) were performed to examine LMNB2 expression levels. LMNB2 short hairpin RNA plasmid or lentivirus was used to deplete the expression of LMNB2 in human TNBC cell lines including MDA-MB-468 and MDA-MB-231. Alterations in cell proliferation and apoptosis in vitro and the nude mouse tumorigenicity assay in vivo were subsequently analyzed. The human TNBC tissues shown high expression of LMNB2 according to the bioinformation analysis and IHC assays. LMNB2 expression was correlated with the clinical pathological features of TNBC patients, including pTNM stage and lymph node metastasis. Through in vitro and in vivo assays, we confirmed LMNB2 depletion suppressed the proliferation and induced the apoptosis of TNBC cells, and inhibited tumor growth of TNBC cells in mice, with the decrease in Ki67 expression or the increase in caspase-3 expression. In conclusion, LMNB2 may promote TNBC progression and could serve as a potential therapeutic target for TNBC treatment.

scholarly journals Dezocine, An Opioid Analgesic, Exerts Antitumor Effects in Triple-Negative Breast Cancer by Targeting Nicotinamide Phosphoribosyltransferase

2021 ◽  
Vol 12 ◽  
Author(s):  
Chenyang Xue ◽  
Wei Chen ◽  
Aiwu Yuan ◽  
Cheng Chen ◽  
Shuaihu Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Progression ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Opioid Analgesic ◽  
Migration And Invasion ◽  
Antitumor Effects ◽  
Nicotinamide Phosphoribosyltransferase

Opioids are a potential adjuvant treatment for certain cancers; while they are primarily used to relieve chronic pain, these drugs may also affect cancer progression and recurrence. Dezocine is one opioid commonly used in China, but its effects on cancer cells are unknown. Here, we demonstrated the inhibitory effect of dezocine on triple-negative breast cancer (TNBC) cells, and determined the underlying molecular mechanism. We found that dezocine suppressed cell proliferation, migration and invasion, and induced apoptosis in TNBC cells. Xenograft models demonstrated the inhibitory effects of dezocine treatment on TNBC tumor growth in vivo. The anticancer effects of dezocine were independent of opioid receptors, which are not highly expressed by normal breast or breast cancer tissues. A pull-down assay and LC-MS/MS analysis indicated that dezocine directly targets NAMPT: computer modeling verified that the free energy of dezocine kinetically bound into the pocket of NAMPT was −17.4 kcal/mol. Consequently, dezocine treatment inhibited NAMPT enzyme activity, resulting in cellular NAD abolishment. We confirmed the dezocine-induced inhibition of cell proliferation by both NAMPT knockdown and upon treatment with the inhibitor FK866. Our results suggest that both dezocine and NAMPT might represent novel therapeutic targets for TNBC.

scholarly journals Integrative analysis of mRNA and miRNA profiles identifies miR-193 and miR-210 as potential regulatory biomarkers in different molecular subtypes of breast cancer

2021 ◽  
Author(s):  
Adriane Feijo Evangelista ◽  
Renato J Oliveira ◽  
Viviane A O Silva ◽  
Rene A D C Vieira ◽  
Rui M Reis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Line ◽  
Cell Lines ◽  
Breast Cancer Cell ◽  
Cancer Progression ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
Breast Cancer Cell Lines ◽  
Mcf 7

Abstract Background: Breast cancer is the most frequently diagnosed malignancy among women. However, the role of microRNA (miRNA) expression in breast cancer progression is not fully understood. In this study we examined predictive interactions between differentially expressed miRNAs and mRNAs in breast cancer cell lines representative of the common molecular subtypes. Integrative bioinformatics analysis identified miR-193 and miR-210 as potential regulatory biomarkers of mRNA in breast cancer. Several recent studies have investigated these miRNAs in a broad range of tumors, but the mechanism of their involvement in cancer progression has not previously been investigated.Methods: The miRNA-mRNA interactions in breast cancer cell lines were identified by parallel expression analysis and miRNA target prediction programs. The expression profiles of mRNA and miRNAs from luminal (MCF-7, MCF-7/AZ and T47D), HER2 (BT20 and SK-BR3) and triple negative subtypes (Hs578T e MDA-MB-231) could be clearly separated by unsupervised analysis using HB4A cell line as a control. Breast cancer miRNA data from TCGA patients were grouped according to molecular subtypes and then used to validate these findings. Expression of miR-193 and miR-210 was investigated by miRNA transient silencing assays using the MCF7, BT20 and MDA-MB-231 cell lines. Functional studies included, xCELLigence system, ApoTox-Glo triplex assay, flow cytometry and transwell inserts were performed to determine cell proliferation, cytotoxicity, apoptosis, migration and invasion, respectively.Results: The most evident effects were associated with cell proliferation after miR-210 silencing in triple negative subtype cell line MDA-MB-231. Using in silico prediction algorithms, TNFRSF10 was identified as one of the potential regulated downstream targets for both miRNAs. The TNFRSF10C and TNFRSF10D mRNA expression inversely correlated with the expression levels of miR-193 and miR210 in breast cell lines and breast cancer patients, respectively. Other potential regulated genes whose expression also inversely correlated with both miRNAs were CCND1, a known mediator on invasion and metastasis, and the tumor suppressor gene RUNX3.Conclusions: In summary, our findings identify miR-193 and miR-210 as potential regulatory miRNA in different molecular subtypes of breast cancer and suggest that miR-210 may have a specific role in MDA-MB-231 proliferation. Our results highlight important new downstream regulated targets that may serve as promising therapeutic pathways for aggressive breast cancers

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