FOXP3 Activates SUMO-Conjugating UBC9 Gene in MCF7 Breast Cancer Cells

Forkhead Box Protein P3 (FOXP3), a transcription factor of the FOX protein family, is essentially involved in the development of regulatory T (Treg) cells, and functions as a tumor suppressor. Although FOXP3 has been widely studied in immune system and cancer development, its function in the regulation of the UBC9 gene (for the sole E2 enzyme of SUMOylation) is unknown. Herein, we find that the overexpression of FOXP3 in human MCF7 breast cancer cells increases the level of UBC9 mRNA. Moreover, the level of UBC9 protein dose-dependently increases in the FOXP3-Tet-off MCF7 cells. Notably, the promoter activity of the UBC9 is activated by FOXP3 in a dose-dependent manner in both the MCF7 and HEK293 cells. Next, by mapping the UBC9 promoter as well as the site-directed mutagenesis and ChIP analysis, we show that the FOXP3 response element at the −310 bp region, but not the −2182 bp region, is mainly required for UBC9 activation by FOXP3. Finally, we demonstrate that the removal of phosphorylation (S418A and Y342F) and the removal of acetylation/ubiquitination (K263R and K263RK268R) of the FOXP3 result in attenuated transcriptional activity of UBC9. Taken together, FOXP3 acts as a novel transcriptional activator of the human UBC9 gene, suggesting that FOXP3 may have physiological functions as a novel player in global SUMOylation, as well as other post-translational modification systems.

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ATP Inhibits Breast Cancer Migration and Bone Metastasis through Down-Regulation of CXCR4 and Purinergic Receptor P2Y11

Cancers ◽

10.3390/cancers13174293 ◽

2021 ◽

Vol 13 (17) ◽

pp. 4293

Author(s):

Xiaowen Liu ◽

Manuel A. Riquelme ◽

Yi Tian ◽

Dezhi Zhao ◽

Francisca M. Acosta ◽

...

Keyword(s):

Breast Cancer ◽

Cell Migration ◽

Bone Metastasis ◽

Cancer Cells ◽

Cancer Cell ◽

Breast Cancer Cells ◽

Cxcr4 Expression ◽

Dependent Manner ◽

Cancer Cell Migration ◽

Dose Dependent

ATP released by bone osteocytes is shown to activate purinergic signaling and inhibit the metastasis of breast cancer cells into the bone. However, the underlying molecular mechanism is not well understood. Here, we demonstrate the important roles of the CXCR4 and P2Y11 purinergic receptors in mediating the inhibitory effect of ATP on breast cancer cell migration and bone metastasis. Wound-healing and transwell migration assays showed that non-hydrolysable ATP analogue, ATPγS, inhibited migration of bone-tropic human breast cancer cells in a dose-dependent manner. BzATP, an agonist for P2X7 and an inducer for P2Y11 internalization, had a similar dose-dependent inhibition on cell migration. Both ATPγS and BzATP suppressed the expression of CXCR4, a chemokine receptor known to promote breast cancer bone metastasis, and knocking down CXCR4 expression by siRNA attenuated the inhibitory effect of ATPγS on cancer cell migration. While a P2X7 antagonist A804598 had no effect on the impact of ATPγS on cell migration, antagonizing P2Y11 by NF157 ablated the effect of ATPγS. Moreover, the reduction in P2Y11 expression by siRNA decreased cancer cell migration and abolished the impact of ATPγS on cell migration and CXCR4 expression. Similar to the effect of ATPγS on cell migration, antagonizing P2Y11 inhibited bone-tropic breast cancer cell migration in a dose-dependent manner. An in vivo study using an intratibial bone metastatic model showed that ATPγS inhibited breast cancer growth in the bone. Taken together, these results suggest that ATP inhibits bone-tropic breast cancer cells by down-regulating the P2Y11 purinergic receptor and the down-regulation of CXCR4 expression.

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Cytotoxic, Anti-Migration, and Anti-Invasion Activities on Breast Cancer Cells of Angucycline Glycosides Isolated from a Marine-Derived Streptomyces sp.

Marine Drugs ◽

10.3390/md17050277 ◽

2019 ◽

Vol 17 (5) ◽

pp. 277 ◽

Cited By ~ 5

Author(s):

Xin-Ying Qu ◽

Jin-Wei Ren ◽

Ai-Hong Peng ◽

Shi-Qi Lin ◽

Dan-Dan Lu ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Ring Cleavage ◽

Migration And Invasion ◽

Dependent Manner ◽

Streptomyces Sp ◽

Deoxy Sugar ◽

Ic50 Values ◽

Dose Dependent

Four angucycline glycosides were previously characterized from marine-derived Streptomyces sp. OC1610.4. Further investigation of this strain cultured on different fermentation media from that used previously resulted in the isolation of two new angucycline glycosides, vineomycins E and F (1–2), and five known homologues, grincamycin L (3), vineomycinone B2 (4), fridamycin D (5), moromycin B (7), and saquayamycin B1 (8). Vineomycin F (2) contains an unusual ring-cleavage deoxy sugar. All the angucycline glycosides isolated from Streptomyces sp. OC1610.4 were evaluated for their cytotoxic activity against breast cancer cells MCF-7, MDA-MB-231, and BT-474. Moromycin B (7), saquayamycin B1 (8), and saquayamycin B (9) displayed potent anti-proliferation against the tested cell lines, with IC50 values ranging from 0.16 to 0.67 μM. Saquayamycin B (9) inhibited the migration and invasion of MDA-MB-231 cells in a dose-dependent manner, as detected by Transwell and wound-healing assays.

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Differential Procoagulant Phenotype of Pancreatic and Breast Cancer Cells Related to Different Tissue Factor Activity.

Blood ◽

10.1182/blood.v110.11.3992.3992 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3992-3992

Author(s):

Grigoris T. Gerotziafas ◽

Ismail Elalamy ◽

Marie-Paule Roman ◽

Claudine Prengel ◽

Elisabeth Verdy ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Tissue Factor ◽

Breast Cancer Cells ◽

Thrombin Generation ◽

Human Platelet ◽

Procoagulant Activity ◽

Dependent Manner ◽

Mcf7 Cells ◽

Platelet Poor Plasma

Abstract Tissue factor (TF) expressed by some cancer cells is implicated in metastasis and angiogenesis. The influence of cancer cells on blood coagulation has not been adequately studied. We evaluated the procoagulant potential of pancreatic and breast cancer cells (BXPC3 and MCF7 cell lines respectively) when they are in contact with human platelet-poor plasma (PPP). At 40% and 90% confluence, adhesive cultures of BXPC3 and MCF7 cells were treated with trypsine according to standardized procedure and cancer cells were suspended in normal human platelet poor plasma (PPP) at increasing concentrations. Coagulation was triggered by CaCl2 addition and thrombin generation (TG) was monitored using the Calibrated Automated Thrombogram-Thrombinoscope® (Biodis-France). In some experiments, cancer cells were incubated for 30 min with a polyclonal specific anti-TF antibody (American Diagnostics). Cancer cells accelerated TG by decreasing significantly lag-time, and time to Peak of thrombin (ttPeak) but they did not significantly influence the endogenous thrombin potential. BXPC3 had significantly more potent procoagulant activity compared to MCF7 cells. Incubation of cancer cells with anti-TF antibody resulted in a concentration dependent inhibition of their procoagulant effect. The IC50 of the anti-TF antibody for TG induced by BXPC3 was about 10-fold higher to that for MCF7. Pancreatic cancer cells (BXPC3) and breast cancer cells (MCF7) accelerate thrombin generation of human plasma in a TF-dependent manner. BXPC3 have more potent procoagulant activity than MCF7 probably due to increased TF expression.

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EphB4 Tyrosine Kinase Stimulation Inhibits Growth of MDA-MB-231 Breast Cancer Cells in a Dose and Time Dependent Manner

Disease Markers ◽

10.1155/2013/857895 ◽

2013 ◽

Vol 35 ◽

pp. 933-938 ◽

Cited By ~ 7

Author(s):

Farnaz Barneh ◽

Mona Moshayedi ◽

Hamid Mirmohammadsadeghi ◽

Shaghayegh Haghjooy-Javanmard ◽

Ali Mohammad Sabzghabaee ◽

...

Keyword(s):

Breast Cancer ◽

Tyrosine Kinase ◽

Cell Viability ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Dependent Manner ◽

Growth Inhibitory ◽

Therapeutic Value ◽

Dose Dependent ◽

Stimulation Of

Background. EphB4 receptor tyrosine kinase is of diagnostic and therapeutic value due to its overexpression in breast tumors. Dual functions of tumor promotion and suppression have been reported for this receptor based on presence or absence of its ligand. To elucidate such discrepancy, we aimed to determine the effect of time- and dose-dependent stimulation of EphB4 on viability and invasion of breast cancer cells via recombinant ephrinB2-Fc.Methods. Cells were seeded into multiwell plates and were stimulated by various concentrations of preclustered ephrinB2-Fc. Cell viability was measured on days 3 and 6 following treatment using alamar-blue when cells were in different states of confluence.Results. Stimulation of cells with ephrinB2 did not pose any significant effect on cell viability before reaching confluence, while inhibition of cell growth was detected after 6 days when cells were in postconfluent state following a dose-dependent manner. EphrinB2 treatment did not affect tubular formation and invasion on matrigel.Conclusion. This study showed that EphB4 can differentially inhibit cells at post confluent state and that presence of ligand manifests growth-inhibitory properties of EphB4 receptor. It is concluded that growth inhibition has occurred possibly due to long treatment with ligand, a process which leads to receptor downregulation.

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Overexpression of the urokinase receptor splice variant uPAR-del4/5 in breast cancer cells affects cell adhesion and invasion in a dose-dependent manner and modulates transcription of tumor-associated genes

Biological Chemistry ◽

10.1515/hsz-2012-0206 ◽

2012 ◽

Vol 393 (12) ◽

pp. 1449-1455 ◽

Cited By ~ 5

Author(s):

Bettina Grismayer ◽

Sumito Sato ◽

Charlotte Kopitz ◽

Christian Ries ◽

Susanne Soelch ◽

...

Keyword(s):

Breast Cancer ◽

Cell Adhesion ◽

Cancer Cells ◽

Splice Variant ◽

Breast Cancer Cells ◽

Urokinase Receptor ◽

Mrna Levels ◽

Dependent Manner ◽

Dose Dependent ◽

Adhesion And Invasion

Abstract mRNA levels of the urokinase receptor splice variant uPAR-del4/5 are associated with prognosis in breast cancer. Its overexpression in cancer cells affects tumor biologically relevant processes. In the present study, individual breast cancer cell clones displaying low vs. high uPAR-del4/5 expression were analyzed demonstrating that uPAR-del4/5 leads to reduced cell adhesion and invasion in a dose-dependent manner. Additionally, matrix metalloproteinase-9 (MMP-9) was found to be strongly upregulated in uPAR-del4/5 overexpressing compared to vector control cells. uPAR-del4/5 may thus play an important role in the regulation of the extracellular proteolytic network and, by this, influence the metastatic potential of breast cancer cells.

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Cytotoxicity of Biologically Synthesized Silver Nanoparticles in MDA-MB-231 Human Breast Cancer Cells

BioMed Research International ◽

10.1155/2013/535796 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 136

Author(s):

Sangiliyandi Gurunathan ◽

Jae Woong Han ◽

Vasuki Eppakayala ◽

Muniyandi Jeyaraj ◽

Jin-Hoi Kim

Keyword(s):

Breast Cancer ◽

Silver Nanoparticles ◽

Cancer Cells ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Ros Generation ◽

Dependent Manner ◽

Limited Information ◽

Human Breast ◽

Dose Dependent

Silver nanoparticles (AgNPs) have been used as an antimicrobial and disinfectant agents. However, there is limited information about antitumor potential. Therefore, this study focused on determining cytotoxic effects of AgNPs on MDA-MB-231 breast cancer cells and its mechanism of cell death. Herein, we developed a green method for synthesis of AgNPs using culture supernatant ofBacillus funiculus, and synthesized AgNPs were characterized by various analytical techniques such as UV-visible spectrophotometer, particle size analyzer, and transmission electron microscopy (TEM). The toxicity was evaluated using cell viability, metabolic activity, and oxidative stress. MDA-MB-231 breast cancer cells were treated with various concentrations of AgNPs (5 to 25 μg/mL) for 24 h. We found that AgNPs inhibited the growth in a dose-dependent manner using MTT assay. AgNPs showed dose-dependent cytotoxicity against MDA-MB-231 cells through activation of the lactate dehydrogenase (LDH), caspase-3, reactive oxygen species (ROS) generation, eventually leading to induction of apoptosis which was further confirmed through resulting nuclear fragmentation. The present results showed that AgNPs might be a potential alternative agent for human breast cancer therapy.

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Anticancer Activities of Phlogacanthus pulcherrimus T. Anderson Leaves Extract on MCF-7 Breast Cancer Cells

Key Engineering Materials ◽

10.4028/www.scientific.net/kem.901.16 ◽

2021 ◽

Vol 901 ◽

pp. 16-21

Author(s):

Supavadee Boontha ◽

Benjaporn Buranrat ◽

Prapapan Temkitthawon ◽

Tasana Pitaksuteepong

Keyword(s):

Breast Cancer ◽

Cell Migration ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Leaf Extract ◽

Dependent Manner ◽

Ros Formation ◽

Dose Dependent ◽

Ethanolic Leaf Extract ◽

Mcf 7

Phlogacanthus pulcherrimus T. Anderson (PPT) is an edible plant found in the northern and northeastern regions of Thailand. There is limited information about the anti-breast cancer activity of the ethanolic leaf extract of PPT. This study aimed to evaluate the effects of an ethanolic leaf extract of PPT on MCF-7 breast cancer cell lines. The biological effects, including cytotoxicity, cell apoptosis, colony formation, reactive oxygen species (ROS) formation and cell migration, were determined by a means of sulforhodamine B (SRB), acridine orange/ethidium bromide (AO/EB) staining, a clonogenic assay, flow cytometry and a scratch wound healing assay, respectively. The results demonstrated that the PPT extract showed cytotoxic on MCF-7 cells in a dose-dependent manner with 50% inhibitory concentration (IC50) values of 119.9 ± 12.1 and 51.3 ± 4.7 μg/mL at 24 h and 48 h incubation, respectively. In addition, the extract exhibited cell apoptosis in a dose-dependent manner when used at a concentration of 50–100 μg/mL and inhibited colony formation with an IC50 value of 26.0 ± 2.0 μg/mL when compared with the control group. The extract induced ROS formation in a dose-dependent manner when used at a concentration of 50–100 μg/mL. The extract suppressed MCF-7 cell migration, with significant effect at 25 μg/mL. These results indicate that PPT ethanolic leaf extract has an anticancer activity against MCF-7 breast cancer cells and may be useful for prevention and treatment of breast cancer.

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Arginine Methyltransferase PRMT1 Regulates p53 Activity in Breast Cancer

Life ◽

10.3390/life11080789 ◽

2021 ◽

Vol 11 (8) ◽

pp. 789

Author(s):

Li-Ming Liu ◽

Qiang Tang ◽

Xin Hu ◽

Jing-Jing Zhao ◽

Yuan Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Cell Growth ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Asymmetric Dimethylarginine ◽

Human Cancer ◽

Specific Inhibitor ◽

Dependent Manner ◽

Breast Tumorigenesis ◽

Stress Signals

The protein p53 is one of the most important tumor suppressors, responding to a variety of stress signals. Mutations in p53 occur in about half of human cancer cases, and dysregulation of the p53 function by epigenetic modifiers and modifications is prevalent in a large proportion of the remainder. PRMT1 is the main enzyme responsible for the generation of asymmetric-dimethylarginine, whose upregulation or aberrant splicing has been observed in many types of malignancies. Here, we demonstrate that p53 function is regulated by PRMT1 in breast cancer cells. PRMT1 knockdown activated the p53 signal pathway and induced cell growth-arrest and senescence. PRMT1 could directly bind to p53 and inhibit the transcriptional activity of p53 in an enzymatically dependent manner, resulting in a decrease in the expression levels of several key downstream targets of the p53 pathway. We were able to detect p53 asymmetric-dimethylarginine signals in breast cancer cells and breast cancer tissues from patients, and the signals could be significantly weakened by silencing of PRMT1 with shRNA, or inhibiting PRMT1 activity with a specific inhibitor. Furthermore, PRMT1 inhibitors significantly impeded cell growth and promoted cellular senescence in breast cancer cells and primary tumor cells. These results indicate an important role of PRMT1 in the regulation of p53 function in breast tumorigenesis.

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Comparative effect of thermo/pH-responsive polymer-coated gold nanocages and hollow nanostars on chemo-photothermal therapy of breast cancer cells

Cancer Nanotechnology ◽

10.1186/s12645-021-00091-x ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Asrin Pakravan ◽

Mehdi Azizi ◽

Fariborz Rahimi ◽

Farhad Bani ◽

Farideh Mahmoudzadeh ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Mtt Assay ◽

Photothermal Therapy ◽

Breast Cancer Cells ◽

Covalent Attachment ◽

Mcf7 Cells ◽

Dapi Staining ◽

Hemolysis Assay ◽

Gold Nanocages

Abstract Background Combination chemo-photothermal therapy appears to be one of the next generations of cancer treatment. In this study hollow gold nanostars (HGNSs) and gold nanocages (GNCs) were synthesized and stabilized with thermo-pH-sensitive thiol-end capped ABC triblock copolymer poly(acrylic acid)-b-poly(N isopropylacrylamide)-b-poly (e-caprolactone)-SH; PAA-b-PNIPAAm-b-PCL-SH (GNSs@Pol). Doxorubicin (Dox) was conjugated to the GNSs@Pol nanostructures via ionic interaction, covalent attachment and hydrogen bonding (GNSs@Dox-Pol). The physicochemical characteristics of prepared GNSs@Pol and GNSs were assessed using dynamic light scattering (DLS), transmission electron microscopy (TEM) and zeta potential techniques. Cytocompatibility of the GNSs@Pol was studied by hemolysis assay and MTT assay. The chemo-photothermal therapy (PTT) potential of GNSs@Dox-Pol was compared on MCF7 cells using MTT assay, cell cycle, DAPI staining and Annexin-V apoptosis assay techniques. Results Cell internalization results showed an almost complete uptake of GNSs@Pol by MCF-7 cells in the first 3 h of treatment. The heat generation measurement results showed that both of GNSs have a potential for light to heat conversion (∆T = 23–27 ºC) and HGNSs demonstrated better efficiency than GNCs after 10-min exposure to NIR irradiation. Following chemo-photothermal treatment, the highest cell mortality (90%) and apoptotic effects (97% apoptosis) were observed in HGNSs@Dox-Pol received laser irradiation treatment group. Conclusions This work highlights the potential application of designed GNSs@Dox-Pol in a combinational chemo-PTT to treat breast cancer cells. Graphic abstract

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