scholarly journals The Secretome of Human Neonatal Mesenchymal Stem Cells Modulates Doxorubicin-Induced Cytotoxicity: Impact in Non-Tumor Cells

2021 ◽  
Vol 22 (23) ◽  
pp. 13072
Author(s):  
Ana S. Serras ◽  
Sérgio P. Camões ◽  
Bernardo Antunes ◽  
Vera M. Costa ◽  
Flávio Dionísio ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Proteomic Analysis ◽  
Underlying Mechanism ◽  
Breast Epithelial Cells ◽  
Malignant Breast ◽  
Breast Cells ◽  
Potential Use ◽  
Target Side ◽  
Chemotherapy Adjuvant ◽  
Target Effects

Doxorubicin (Dox) is one of the most widely used treatments for breast cancer, although limited by the well-documented cardiotoxicity and other off-target effects. Mesenchymal stem cell (MSC) secretome has shown immunomodulatory and regenerative properties, further potentiated under 3D conditions. This work aimed to uncover the effect of the MSC-derived secretome from 3D (CM3D) or 2D (CM2D) cultures, in human malignant breast cells (MDA-MB-231), non-tumor breast epithelial cells (MCF10A) and differentiated AC16 cardiomyocytes, co-treated with Dox. A comprehensive proteomic analysis of CM3D/CM2D was also performed to unravel the underlying mechanism. CM3D/CM2D co-incubation with Dox revealed no significant differences in MDA-MB-231 viability when compared to Dox alone, whereas MCF10A and AC16 viability was consistently improved in Dox+CM3D-treated cells. Moreover, neither CM2D nor CM3D affected Dox anti-migratory and anti-invasive effects in MDA-MB-231. Notably, Ge-LC-MS/MS proteomic analysis revealed that CM3D displayed protective features that might be linked to the regulation of cell proliferation (CAPN1, CST1, LAMC2, RANBP3), migration (CCN3, MMP8, PDCD5), invasion (TIMP1/2), oxidative stress (COX6B1, AIFM1, CD9, GSR) and inflammation (CCN3, ANXA5, CDH13, GDF15). Overall, CM3D decreased Dox-induced cytotoxicity in non-tumor cells, without compromising Dox chemotherapeutic profile in malignant cells, suggesting its potential use as a chemotherapy adjuvant to reduce off-target side effects.

Transferrin-Conjugated Nanocarriers as Active-Targeted Drug Delivery Platforms for Cancer Therapy

2017 ◽  
Vol 23 (3) ◽  
pp. 454-466 ◽  
Author(s):  
Daniele R. Nogueira-Librelotto ◽  
Cristiane F. Codevilla ◽  
Ammad Farooqi ◽  
Clarice M. B. Rolim
Keyword(s):  
Drug Delivery ◽  
Cancer Therapy ◽  
Tumor Cells ◽  
Therapeutic Benefit ◽  
Active Targeting ◽  
Future Research ◽  
Passive Targeting ◽  
The Right ◽  
Review Current ◽  
Target Effects

A lot of effort has been devoted to achieving active targeting for cancer therapy in order to reach the right cells. Hence, increasingly it is being realized that active-targeted nanocarriers notably reduce off-target effects, mainly because of targeted localization in tumors and active cellular uptake. In this context, by taking advantage of the overexpression of transferrin receptors on the surface of tumor cells, transferrin-conjugated nanodevices have been designed, in hope that the biomarker grafting would help to maximize the therapeutic benefit and to minimize the side effects. Notably, active targeting nanoparticles have shown improved therapeutic performances in different tumor models as compared to their passive targeting counterparts. In this review, current development of nano-based devices conjugated with transferrin for active tumor-targeting drug delivery are highlighted and discussed. The main objective of this review is to provide a summary of the vast types of nanomaterials that have been used to deliver different chemotherapeutics into tumor cells, and to ultimately evaluate the progression on the strategies for cancer therapy in view of the future research.

scholarly journals The T Box Transcription Factor TBX2 Promotes Epithelial-Mesenchymal Transition and Invasion of Normal and Malignant Breast Epithelial Cells

PLoS ONE ◽  
2012 ◽  
Vol 7 (7) ◽  
pp. e41355 ◽  
Author(s):  
Bin Wang ◽  
Linsey E. Lindley ◽  
Virneliz Fernandez-Vega ◽  
Megan E. Rieger ◽  
Andrew H. Sims ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Epithelial Cells ◽  
Epithelial Mesenchymal Transition ◽  
Breast Epithelial Cells ◽  
Mesenchymal Transition ◽  
T Box ◽  
Malignant Breast ◽  
Breast Epithelial

scholarly journals Hydrogen Sulfide Protects Cardiomyocytes against Apoptosis in Ischemia/Reperfusion through MiR-1-Regulated Histone Deacetylase 4 Pathway

2016 ◽  
Vol 41 (1) ◽  
pp. 10-21 ◽  
Author(s):  
Bo Kang ◽  
Wei Li ◽  
Wang Xi ◽  
Yinghong Yi ◽  
Yundan Ciren ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Protective Effect ◽  
Signaling Pathway ◽  
Tumor Cells ◽  
Histone Deacetylase ◽  
Caspase 3 ◽  
Ischemia Reperfusion ◽  
Underlying Mechanism ◽  
Neonatal Rats ◽  
Histone Deacetylase 4

Background/Aims: Hydrogen sulfide (H<Sub>2</Sub>S) is a powerful inhibitor of cardiomyocytes apoptosis following ischemia/reperfusion (IR) injury, but the underlying mechanism remains unclear. Our previous study showed that microRNA-1 (miR-1) was upregulated by 2.21 fold in the IR group compared with that in the H<Sub>2</Sub>S preconditioned group. MiR-206 affected the process of cardiomyocytes hypertrophy by regulating histone deacetylase 4 (HDAC4). HDAC4 is also known to play an anti-apoptotic role in tumor cells, but its role in the myocardium has not been reported. The aim of this study was to test whether H<Sub>2</Sub>S could inhibit apoptosis of cardiomyocytes through HDAC4 regulation by miR-1 in IR. Methods: Cardiomyocytes of neonatal rats were subjected to hypoxia/reoxygenation (HR) injury with or without H<Sub>2</Sub>S pretreatment to simulate IR injury Cardiomyocytes were transfected with miR-1 mimic or HDAC4 siRNA to evaluate whether the miR-1-HDAC4 signaling pathway was involved in the protective effect of H<Sub>2</Sub>S. Results: HR increased cell apoptosis and caspase-3 cleavage, upregulated miR-1, and downregulated HDAC4. H<Sub>2</Sub>S preconditioning attenuated the apoptosis of cardiomyocytes, caspase-3 cleavage and LDH release, and enhanced cell viability In addition, H<Sub>2</Sub>S downregulated miR-1, and preserved HDAC4 expression. HDAC4 protein was down-regulated by miR-1 mimic. Transfection of cardiomyocytes with miR-1 mimic partially reduced the protective effect of H<Sub>2</Sub>S. Meanwhile, transfection of cardiomyocytes with siRNA to HDAC4 partially abrogated the protective effect of H<Sub>2</Sub>S. Conclusions: The miR-1-HDAC4 signaling pathway is involved in the protective effect of H<Sub>2</Sub>S against the apoptosis of cardiomyocytes during the IR injury process.

Detection of Premalignant and Malignant Breast Cells by Ductal Lavage

2001 ◽  
Vol 97 (Supplement) ◽  
pp. 2S
Author(s):  
William C. Dooley ◽  
U. Veronesi ◽  
R. Elledge ◽  
J. OʼShaughnessy ◽  
B-M Ljung ◽  
...  
Keyword(s):  
Ductal Lavage ◽  
Malignant Breast ◽  
Breast Cells

Increased MAGEC2 Expression Renders Resistance to Apoptotic Death Through Sustained Activation of STAT3 in Suspension Cultured Tumor Cells

2020 ◽  
Author(s):  
Doyeon Park ◽  
Sora Han ◽  
Hyun Jeong Joo ◽  
Hye In Ka ◽  
Su Jung Soh ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Apoptotic Cell ◽  
Annexin V ◽  
Underlying Mechanism ◽  
Proliferation Rate ◽  
Suspension Cells ◽  
Protein Levels ◽  
Proliferation And Apoptosis ◽  
Cancer Types

Abstract Background Melanoma-associated antigen C2 (MAGEC2) is an oncogene associated with various cancer types. However, the biological function of MAGEC2 in circulating tumor cells is unclear. In this study, we investigated the role of MAGEC2 using adapted suspension cells (ASCs), which were previously developed to study circulating tumor cells (CTCs).Methods Differential gene expression between adherent cells (ADs) and ASCs was examined using RNA-seq analysis. MAGEC2 expression was assessed using RT-qPCR, immunoblotting, and ChIP-seq analysis. Depletion of MAGEC2 expression was carried out using siRNA. MAGEC2-depleted ADs and ASCs were used to investigate the change in proliferation rate and cell cycle. Then, the protein levels of STAT3, phosphorylated STAT3, and downstream of STAT3 were measured using control and MAGEC2-depleted ADs and ASCs. The direct effect of active STAT3 inhibition with Stattic in ASCs was also assessed in terms of proliferation and apoptosis. Finally, an Annexin V/7-AAD assay was performed to determine the percentage of apoptotic cells in Stattic-treated cells. Results MAGEC2 was highly expressed in ASCs compared to ADs. Depletion of MAGEC2 reduced the proliferation rate and viability of ASCs. To elucidate the underlying mechanism, the level of STAT3 was examined because of its oncogenic properties. Tyrosine-phosphorylated active STAT3 was highly expressed in ASCs and decreased in MAGEC2-depleted ASCs. In addition, when ASCs were treated with Stattic, an active STAT3 inhibitor, they were more sensitive to intrinsic pathway-mediated apoptosis.Conclusions High expression of MAGEC2 may play an important role in the survival of ASCs by maintaining the expression of activated STAT3 to prevent apoptotic cell death.

scholarly journals Radiation Induced Upregulation of DNA Sensing Pathways is Cell-Type Dependent and Can Mediate the Off-Target Effects

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3365
Author(s):  
Tanja Jesenko ◽  
Masa Bosnjak ◽  
Bostjan Markelc ◽  
Gregor Sersa ◽  
Katarina Znidar ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Checkpoint Inhibitors ◽  
Cell Types ◽  
Immunofluorescent Staining ◽  
Dna Sensing ◽  
Radiation Induced ◽  
Underlying Mechanisms ◽  
Sting Pathway ◽  
Abscopal Effects ◽  
Target Effects

Irradiation of tumors generates danger signals and inflammatory cytokines that promote the off-target bystander and abscopal effects, evident especially when radiotherapy is administered in combination with the immune checkpoint inhibitors (ICI). The underlying mechanisms are not fully understood; however, cGAS-STING pathway was recognized as the main mediator. In our study, we demonstrate by immunofluorescent staining that tumor cells as well as macrophages, cell types abundant in the tumor microenvironmeent (TME) accumulate DNA in their cytosol soon after irradiation. This accumulation activated several distinct DNA sensing pathways, most prominently activated DNA sensors being DDX60, DAI, and p204 in tumor cells and DDX60, DAI, p204, and RIG-I in macrophages as determined by PCR and immunofluorescence imaging studies. This was accompanied by increased expression of cytokines evaluated by flow cytometry, TNFα, and IFNβ in tumor cells and IL1β and IFNβ in macrophages, which can alter the TME and mediate off-target effects (bystander or abscopal effects). These results give insight into the mechanisms involved in the stimulation of antitumor immunity by radiation.

scholarly journals Effects of ubiquitin C-terminal hydrolase L1 deficiency on mouse ova

Reproduction ◽  
2012 ◽  
Vol 143 (3) ◽  
pp. 271-279 ◽  
Author(s):  
Sayaka Koyanagi ◽  
Hiroko Hamasaki ◽  
Satoshi Sekiguchi ◽  
Kenshiro Hara ◽  
Yoshiyuki Ishii ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Endoplasmic Reticulum ◽  
Proteomic Analysis ◽  
Ubiquitin Proteasome System ◽  
Underlying Mechanism ◽  
Wild Type ◽  
Transmission Electron ◽  
Ubiquitin Proteasome

Maternal proteins are rapidly degraded by the ubiquitin–proteasome system during oocyte maturation in mice. Ubiquitin C-terminal hydrolase L1 (UCHL1) is highly and specifically expressed in mouse ova and is involved in the polyspermy block. However, the role of UCHL1 in the underlying mechanism of polyspermy block is poorly understood. To address this issue, we performed a comprehensive proteomic analysis to identify maternal proteins that were relevant to the role of UCHL1 in mouse ova using UCHL1-deficientgad. Furthermore, we assessed morphological features ingadmouse ova using transmission electron microscopy. NACHT, LRR, and PYD domain-containing (NALP) family proteins and endoplasmic reticulum (ER) chaperones were identified by proteomic analysis. We also found that the ‘maternal antigen that embryos require’ (NLRP5 (MATER)) protein level increased significantly ingadmouse ova compared with that in wild-type mice. In an ultrastructural study,gadmouse ova contained less ER in the cortex than in wild-type mice. These results provide new insights into the role of UCHL1 in the mechanism of polyspermy block in mouse ova.

Sign in / Sign up

Export Citation Format

Share Document