G-Quadruplex Binders Induce Immunogenic Cell Death Markers in Aggressive Breast Cancer Cells

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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Force-dependent trans-endocytosis by breast cancer cells depletes costimulatory receptor CD80 and attenuates T cell activation

Biosensors and Bioelectronics ◽

10.1016/j.bios.2020.112389 ◽

2020 ◽

Vol 165 ◽

pp. 112389 ◽

Cited By ~ 1

Author(s):

Seungman Park ◽

Yu Shi ◽

Byoung Choul Kim ◽

Myung Hyun Jo ◽

Leilani O. Cruz ◽

...

Keyword(s):

Breast Cancer ◽

T Cell ◽

Cancer Cells ◽

T Cell Activation ◽

Breast Cancer Cells ◽

Cell Activation ◽

Costimulatory Receptor

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Laser nanobubbles induce immunogenic cell death in breast cancer

Nanoscale ◽

10.1039/d0nr06587k ◽

2021 ◽

Vol 13 (6) ◽

pp. 3644-3653

Author(s):

Hieu T. M. Nguyen ◽

Nitesh Katta ◽

Jessica A. Widman ◽

Eri Takematsu ◽

Xu Feng ◽

...

Keyword(s):

Breast Cancer ◽

Cell Death ◽

Dendritic Cell ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Cell Activation ◽

Immunogenic Cell Death ◽

Dendritic Cell Activation

Laser nanobubbles induce dendritic cell activation in breast cancer cells.

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RPF101, a new capsaicin-like analogue, disrupts the microtubule network accompanied by arrest in the G2/M phase, inducing apoptosis and mitotic catastrophe in the MCF-7 breast cancer cells

Toxicology and Applied Pharmacology ◽

10.1016/j.taap.2012.11.029 ◽

2013 ◽

Vol 266 (3) ◽

pp. 385-398 ◽

Cited By ~ 24

Author(s):

Paulo Luiz de-Sá-Júnior ◽

Kerly Fernanda Mesquita Pasqualoto ◽

Adilson Kleber Ferreira ◽

Maurício Temotheo Tavares ◽

Mariana Celestina Frojuello Damião ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Mitotic Catastrophe ◽

Microtubule Network ◽

M Phase ◽

Mcf 7

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A Flavone Constituent from Myoporum bontioides Induces M-Phase Cell Cycle Arrest of MCF-7 Breast Cancer Cells

Molecules ◽

10.3390/molecules22030472 ◽

2017 ◽

Vol 22 (3) ◽

pp. 472 ◽

Cited By ~ 5

Author(s):

Jing-Ru Weng ◽

Li-Yuan Bai ◽

Wei-Yu Lin ◽

Chang-Fang Chiu ◽

Yu-Chang Chen ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Phase Cell ◽

Cycle Arrest ◽

M Phase ◽

Mcf 7

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Mesenchymal stromal cell activation by breast cancer secretomes in bioengineered 3D microenvironments

Life Science Alliance ◽

10.26508/lsa.201900304 ◽

2019 ◽

Vol 2 (3) ◽

pp. e201900304 ◽

Cited By ~ 6

Author(s):

Ulrich Blache ◽

Edward R Horton ◽

Tian Xia ◽

Erwin M Schoof ◽

Lene H Blicher ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Cancer Progression ◽

Stromal Cells ◽

Breast Cancer Cells ◽

Cell Activation ◽

Tumour Microenvironment ◽

Paracrine Signalling ◽

Organ Specific ◽

Mcf 7

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.

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

Vaccines ◽

10.3390/vaccines7040198 ◽

2019 ◽

Vol 7 (4) ◽

pp. 198 ◽

Cited By ~ 1

Author(s):

Sitti Rahma Abdul Hafid ◽

Ammu Kutty Radhakrishnan

Keyword(s):

Breast Cancer ◽

Dendritic Cells ◽

Cancer Cells ◽

T Cell Activation ◽

Peripheral Blood ◽

Breast Cancer Cells ◽

Cell Activation ◽

Tumor Tissue ◽

Survival Rates ◽

Dc Vaccine

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.

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Target-dependent T-cell Activation by Coligation With a PSMA×CD3 Diabody Induces Lysis of Prostate Cancer Cells

Journal of Immunotherapy ◽

10.1097/cji.0b013e3181a697eb ◽

2009 ◽

Vol 32 (6) ◽

pp. 565-573 ◽

Cited By ~ 21

Author(s):

Patrick Bühler ◽

Eszter Molnar ◽

Elaine P. Dopfer ◽

Philipp Wolf ◽

Dorothee Gierschner ◽

...

Keyword(s):

Prostate Cancer ◽

T Cell ◽

Cancer Cells ◽

T Cell Activation ◽

Cell Activation ◽

Prostate Cancer Cells

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Lidocaine Inhibits Breast Cancer Cell Proliferation and Induces Cell Apoptosis via Regulating MEK/ERK and PI3K/AKT Signalling Pathways

10.21203/rs.3.rs-617189/v1 ◽

2021 ◽

Author(s):

Xu Wang ◽

Shi-Hang Xi ◽

Qin Li ◽

ting han

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Flow Cytometric Analysis ◽

Inhibitory Effect ◽

Potential Candidate ◽

Protein Levels ◽

M Phase ◽

Mcf 7

Abstract Background: Lidocaine is a commonly used local anesthetic in clinic, which is mainly used for anesthesia and analgesia. Lidocaine has been recently found to have an inhibitory effect on a variety of cancers.Materials and Methods: We used MTT assay and cell proliferation assay to detect the inhibition of lidocaine on proliferation of MCF-7 and MDA-MB-231 breast cancer cells. Flow cytometric analysis was used to detect cell cycle and apoptosis. Western blot was used to detect protein levels of cyclin-dependent kinase 1(CDK1) ,cyclinB1, BCL2, BCL-XL, p62, LC3B, p-ERK,p-AKT, ERK and AKT.Results: Lidocaine inhibited the proliferation of MCF-7 and MDA-MB-231 breast cancer cells, increased the percentage of G2 / M phase cells , apoptosis and autophagy by reducing the mRNA of CDK1 and cyclinB1, decreasing protein levels of CDK1,cyclinB1,BCL2, BCL-XL, p62, p-ERK and p-AKT protein, and increasing LC3B-II/LC3B-I protein levels.Conclusion: Lidocaine may be a potential candidate for treatment of breast cancer.

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Phase I study of AMG 757, a half-life extended bispecific T-cell engager (HLE BiTE immune therapy) targeting DLL3, in patients with small cell lung cancer (SCLC).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.tps9080 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. TPS9080-TPS9080

Author(s):

Taofeek Kunle Owonikoko ◽

Hossein Borghaei ◽

Stéphane Champiat ◽

Luis G. Paz-Ares ◽

Ramaswamy Govindan ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Antitumor Activity ◽

Cancer Cells ◽

Tumor Cells ◽

T Cell Activation ◽

Cell Activation ◽

Phase 1 ◽

Immune Therapy ◽

Platinum Based Chemotherapy

TPS9080 Background: SCLC is an aggressive neuroendocrine tumor with poor prognosis and few treatment options. Delta-like ligand 3 (DLL3) is an inhibitory Notch ligand that is highly expressed on the surface of most SCLC tumors but minimally expressed in normal tissues. As such, DLL3 may be a promising therapeutic target. AMG 757 is an HLE BiTE immune therapy designed to redirect cytotoxic T cells to cancer cells by binding to DLL3 on cancer cells and CD3 on T cells, resulting in T cell activation and expansion and T cell-dependent killing of tumor cells. In addition to its direct antitumor effect, BiTE immune therapy can inflame the tumor microenvironment. Combining AMG 757 with a PD-1 pathway inhibitor may lead to increased antitumor activity by enabling sustained T cell-dependent killing of tumor cells. Methods: NCT03319940 is an open-label, ascending, multiple-dose, phase 1 study evaluating AMG 757 as monotherapy; the protocol was recently amended to also evaluate AMG 757 in combination with pembrolizumab. The study will include a dose exploration (monotherapy and combination) followed by a dose expansion (monotherapy). Key eligibility criteria: adult patients with relapsed/refractory SCLC whose disease progressed or recurred after at least 1 platinum-based chemotherapy regimen, ECOG performance status 0–2, at least 2 measurable lesions per modified RECIST 1.1, no untreated or symptomatic brain metastases, and adequate organ function. Primary objectives are to evaluate safety/tolerability and determine the maximum tolerated dose or recommended phase 2 dose of AMG 757 as monotherapy and in combination with pembrolizumab. Secondary objectives are to characterize pharmacokinetics and evaluate preliminary antitumor activity; exploratory objectives are to assess immunogenicity and changes in biomarkers in blood and tumor tissue. In the dose exploration phase, dose escalation/de-escalation decisions will be guided by a Bayesian logistic regression model; backfill enrollment at dose levels deemed safe and tolerable will be allowed. The study is open and recruiting patients. Clinical trial information: NCT03319940.

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