scholarly journals Palm Tocotrienol-Adjuvanted Dendritic Cells Decrease Expression of the SATB1 Gene in Murine Breast Cancer Cells and Tissues

Vaccines ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 198 ◽  
Author(s):  
Sitti Rahma Abdul Hafid ◽  
Ammu Kutty Radhakrishnan

The aim of this study was to evaluate the effectiveness of immunotherapy using dendritic cells (DC) pulsed with tumor lysate (a DC vaccine) in combination with daily supplementation of tocotrienol-rich fraction (TRF) to potentiate anti-tumor immune responses. We had previously reported that DC-vaccine immunotherapy together with TRF supplementation induced protective immunity to tumor challenge. Breast cancer was induced in female BALB/c mice. The mice were randomly assigned into the treatment groups. At autopsy, peripheral blood was collected in heparinized tube and the expression of cell surface molecules (CD40, CD80, CD83, and CD86) that are crucial for T-cell activation and survival were analyzed by flow cytometry. Tumor was excised from each animal and snap-frozen. Total RNA was extracted from each tumor tissue for microarray and gene expression analysis. Total protein was extracted from tumor tissue for protein expression studies using Western blotting. The results show that systemic administration of 1 mg TRF daily in combination with DC-vaccine immunotherapy (DC + TL + TRF) caused a marked reduction (p < 0.05) of tumor size and increased (p < 0.05) the survival rates of the tumor-inoculated mice. The expression of CD40, CD80, CD83, and CD86 were upregulated in peripheral blood from the DC + TL + TRF group compared to other groups. In addition, there was higher expression of FasL in tumor-excised mice from the DC + TL + TRF group compared to other groups. FasL plays an important role in maintaining immune privilege and is required for cytotoxic T-lymphocyte (CTL) activity. Microarray analysis identified several genes involved in the regulation of cancer. In this study, we focused on the special AT rich binding protein 1 (SATB1) gene, which was reported to have dual functions, one of which was to induce aggressive growth in breast cancer cells. Tumors from DC + TL + TRF mice showed lower (p < 0.05) expression of SATB1 gene. Further study will be conducted to investigate the molecular functions of and the role of SATB1 in 4T1 mammary cancer cells and DC. In conclusion, TRF supplementation can potentiate the effectiveness of DC-vaccine immunotherapy.

2020 ◽  
Vol 165 ◽  
pp. 112389 ◽  
Author(s):  
Seungman Park ◽  
Yu Shi ◽  
Byoung Choul Kim ◽  
Myung Hyun Jo ◽  
Leilani O. Cruz ◽  
...  

Nanoscale ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 3644-3653
Author(s):  
Hieu T. M. Nguyen ◽  
Nitesh Katta ◽  
Jessica A. Widman ◽  
Eri Takematsu ◽  
Xu Feng ◽  
...  

Laser nanobubbles induce dendritic cell activation in breast cancer cells.


2003 ◽  
Vol 129 (1) ◽  
pp. 57-64 ◽  
Author(s):  
Yingming Jiang ◽  
Tao Wan ◽  
Guoyou Chen ◽  
Fangming Xiu ◽  
Dajing Xia ◽  
...  

2006 ◽  
Vol 8 (6) ◽  
Author(s):  
Hiroaki Saito ◽  
Peter Dubsky ◽  
Carole Dantin ◽  
Olivera J Finn ◽  
Jacques Banchereau ◽  
...  

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. e12566-e12566 ◽  
Author(s):  
Yong Huang ◽  
Meijun Long ◽  
Jun An ◽  
Mi Tang ◽  
Renbin Liu

2003 ◽  
Vol 107 (6) ◽  
pp. 984-990 ◽  
Author(s):  
José-Juan Gaforio ◽  
María-José Serrano ◽  
Pedro Sanchez-Rovira ◽  
Antonio Sirvent ◽  
Miguel Delgado-Rodriguez ◽  
...  

2019 ◽  
Vol 2 (3) ◽  
pp. e201900304 ◽  
Author(s):  
Ulrich Blache ◽  
Edward R Horton ◽  
Tian Xia ◽  
Erwin M Schoof ◽  
Lene H Blicher ◽  
...  

Mesenchymal stromal cells (MSCs) are key contributors of the tumour microenvironment and are known to promote cancer progression through reciprocal communication with cancer cells, but how they become activated is not fully understood. Here, we investigate how breast cancer cells from different stages of the metastatic cascade convert MSCs into tumour-associated MSCs (TA-MSCs) using unbiased, global approaches. Using mass spectrometry, we compared the secretomes of MCF-7 cells, invasive MDA-MB-231 cells, and sublines isolated from bone, lung, and brain metastases and identified ECM and exosome components associated with invasion and organ-specific metastasis. Next, we used synthetic hydrogels to investigate how these different secretomes activate MSCs in bioengineered 3D microenvironments. Using kinase activity profiling and RNA sequencing, we found that only MDA-MB-231 breast cancer secretomes convert MSCs into TA-MSCs, resulting in an immunomodulatory phenotype that was particularly prominent in response to bone-tropic cancer cells. We have investigated paracrine signalling from breast cancer cells to TA-MSCs in 3D, which may highlight new potential targets for anticancer therapy approaches aimed at targeting tumour stroma.


Author(s):  
Larisa Limareva ◽  
Pavel Iliasov ◽  
Alexander Gidaspov ◽  
Vladimir Zalomlenkov ◽  
Aleksey Sustretov ◽  
...  

2-(Morpholin-4-yl)-4,5-bis(2&rsquo;&rsquo;,2&rsquo;&rsquo;,2&rsquo;&rsquo;-trinitroethoxy)-1,3,5-triazine having QSAR-predicted anti-tumor activity was tested for the cytotoxicity using MTT and LDH cell viability tests. The experiments were conducted using human fibroblasts, peripheral blood mononuclear cells and breast cancer cells and allowed to identify effective cytotoxic concentration ant therapeutic range of this compound. The data obtained suggest the feasibility of the further studies of the test compound as a potential anti-cancer agent.


Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1797 ◽  
Author(s):  
Sarah Di Somma ◽  
Jussara Amato ◽  
Nunzia Iaccarino ◽  
Bruno Pagano ◽  
Antonio Randazzo ◽  
...  

Background: DNA G-quadruplex (G4) structures represent potential anti-cancer targets. In this study, we compared the effect of two G4-targeting compounds, C066-3108 and the gold standard BRACO-19. Methods: In breast and prostate cancer cells, cytotoxicity induced by both molecules was measured by a sulforhodamine B assay. In breast cancer cells, cycle, apoptosis, the formation of G4 structures, calreticulin and high mobility group box 1 (HMGB1), as well as T cell activation, were analyzed by flow cytometry and adenosine triphosphate (ATP) by luminescence. Results: Both ligands inhibited cell survival and induced DNA damage. In MCF-7 cells, G4 ligands increased the subG0/G1 phase of the cell cycle inducing apoptosis and reduced intracellular ATP. In untreated MCF-7 cells, we observed a slight presence of G4 structures associated with the G2/M phase. In MDA-MB231 cells, G4 ligands decreased the G1 and enhanced the G2/M phase. We observed a decrease of intracellular ATP, calreticulin cell surface exposure and an increase of HMGB1, accompanied by T cell activation. Both compounds induced G4 structure formation in the subG0/G1 phase. Conclusions: Our data report similar effects for both compounds and the first evidence that G4 ligands induce the release of danger signals associated with immunogenic cell death and induction of T cell activation.


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