Mechanisms of the anti-tumor activity of Methyl 2-(-5-fluoro-2-hydroxyphenyl)-1 H-benzo[d]imidazole-5-carboxylate against breast cancer in vitro and in vivo

Several studies in the past decades have reported anti-tumor activity of the bioactive compounds extracted from tea leaves, with a focus on the compound epigallocatechin-3-gallate (EGCG). However, further investigations are required to unravel the underlying mechanisms behind the anti-tumor activity of EGCG. In this study, we demonstrate that EGCG significantly inhibits the growth of 4T1 breast cancer cells in vitro and in vivo. EGCG ameliorated immunosuppression by significantly decreasing the accumulation of myeloid-derived suppressor cells (MDSCs) and increasing the proportions of CD4+ and CD8+ T cells in spleen and tumor sites in 4T1 breast tumor-bearing mice. Surprisingly, a low dose of EGCG (0.5–5 μg/mL) effectively reduced the cell viability and increased the apoptosis rate of MDSCs in vitro. EGCG down-regulated the canonical pathways in MDSCs, mainly through the Arg-1/iNOS/Nox2/NF-κB/STAT3 signaling pathway. Moreover, transcriptomic analysis suggested that EGCG also affected the non-canonical pathways in MDSCs, such as ECM–receptor interaction and focal adhesion. qRT-PCR further validated that EGCG restored nine key genes in MDSCs, including Cxcl3, Vcan, Col4a1, Col8a1, Oasl2, Mmp12, Met, Itsnl and Acot1. Our results provide new insight into the mechanism of EGCG-associated key pathways/genes in MDSCs in the murine breast tumor model.

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Abstract S3-6: Combination Therapy of the Novel PI3K Inhibitor GDC-0941 and Dual PI3K/mTOR Inhibitor GDC-0980 with Trastuzumab-DM1 Antibody Drug Conjugate Enhances Anti-Tumor Activity in Preclinical Breast Cancer Models In Vitro and In Vivo

10.1158/0008-5472.sabcs10-s3-6 ◽

2010 ◽

Author(s):

D Sampath ◽

C Fields ◽

G Li ◽

WW Prior ◽

K Parsons ◽

...

Keyword(s):

Breast Cancer ◽

Combination Therapy ◽

Mtor Inhibitor ◽

The Novel ◽

Antibody Drug Conjugate ◽

Cancer Models ◽

Anti Tumor Activity ◽

Antibody Drug

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A Novel Benzocoumarin-Stilbene Hybrid as a DNA ligase I inhibitor with in vitro and in vivo anti-tumor activity in breast cancer models

Scientific Reports ◽

10.1038/s41598-017-10864-3 ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 6

Author(s):

Mohd. Kamil Hussain ◽

Deependra Kumar Singh ◽

Akhilesh Singh ◽

Mohd. Asad ◽

Mohd. Imran Ansari ◽

...

Keyword(s):

Breast Cancer ◽

Dna Ligase ◽

Cancer Models ◽

Dna Ligase I ◽

Anti Tumor Activity

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Osteopontin binds ICOSL promoting tumor metastasis

Communications Biology ◽

10.1038/s42003-020-01333-1 ◽

2020 ◽

Vol 3 (1) ◽

Author(s):

Davide Raineri ◽

Chiara Dianzani ◽

Giuseppe Cappellano ◽

Federica Maione ◽

Gianluca Baldanzi ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Metastasis ◽

Immune Checkpoints ◽

Cancer Model ◽

Therapeutic Approaches ◽

Breast Cancer Model ◽

4T1 Breast Cancer ◽

Anti Tumor Activity

Abstract ICOSL/ICOS are costimulatory molecules pertaining to immune checkpoints; their binding transduces signals having anti-tumor activity. Osteopontin (OPN) is here identified as a ligand for ICOSL. OPN binds a different domain from that used by ICOS, and the binding induces a conformational change in OPN, exposing domains that are relevant for its functions. Here we show that in vitro, ICOSL triggering by OPN induces cell migration, while inhibiting anchorage-independent cell growth. The mouse 4T1 breast cancer model confirms these data. In vivo, OPN-triggering of ICOSL increases angiogenesis and tumor metastatization. The findings shed new light on ICOSL function and indicate that another partner beside ICOS may be involved; they also provide a rationale for developing alternative therapeutic approaches targeting this molecular trio.

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Synthesis of new thioureas derivatives and evaluation of their efficacy as proliferation inhibitors in MCF-7 breast cancer cells by using 99mTc-MIBI radiotracer

Medicinal Chemistry ◽

10.2174/1573406416666200425224921 ◽

2020 ◽

Vol 16 ◽

Author(s):

Ahmad Hormati ◽

Jafar Abbasi Shiran ◽

Mikaeil Molazadeh ◽

Babak Kaboudin ◽

Sajjad Ahmadpour

Keyword(s):

Breast Cancer ◽

Nude Mice ◽

Breast Cancer Cells ◽

Tumor Volume ◽

Tumor Uptake ◽

99Mtc Mibi ◽

Anti Tumor Activity ◽

Mcf 7

Background & objective: Anti-tumor activity of some thioureas derivatives is well documented in literatures and received considerable attention. The present study aims to the synthesis and characterization of some novel thioureas and carbonylthioureas as anti-tumor agents for MCF-7 breast cancer cells in vitro and in vivo. Materials & methods: Several 1-allyl-3-(substituted phenyl), N,N'-(phenylene) bis(3-allyldithithiourea) and 1-cyclopropanecarbonyl-3-(substituted phenyl)-thioureas derivatives were synthesized and confirmed by FT-IR spectroscopy, NMR and 13C-NMR. Anti-tumor activity of these compounds were determined by various in vitro and in vivo assays including; MTT, tumor volume measurement as well as, 99mTc-MIBI tumor uptake in MCF-7 tumor bearing nude mice. Results: Among all of the synthesized compounds, some thioureas derivatives [3i] and [4b] at 100 nM concentration exhibited significant inhibitory effects on the proliferation of MCF-7 cell in vitro. However, this inhibition was not observed in HUVEC human endothelial normal cells. In vivo antitumor effects of the synthesized compounds on MCF-7 xenograft mouse models demonstrated reduction in the tumor volume for various concentrations between 2 to 10 mg/kg after 21 days. These effects were comparable with Tamoxifen as standard anti-estrogen drug. According to the 99mTc-MIBI biodistribution result, treatment of MCF-7 bearing nude mice with both [3i] and [4b] compounds at the maximum concentration (10 mg/kg) can lead to the significant decrease of 99mTc-MIBI tumor uptake. Conclusions: Compounds [3i] and [4b] suppresses the growth of MCF-7 cells in the xenograft nude mice at the doses that were well-tolerated. Our study suggests that these new compounds with their significant anti-tumor effects, may serve as useful candidates for breast cancer therapy.

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