Green Tea Polyphenol EGCG Attenuates MDSCs-mediated Immunosuppression through Canonical and Non-Canonical Pathways in a 4T1 Murine Breast Cancer Model

Xu, Ping; Yan, Feng; Zhao, Yuhai; Chen, Xiangbo; Sun, Shili; Wang, Yuefei; Ying, Le

doi:10.3390/nu12041042

Cited by 53 publications

(35 citation statements)

References 57 publications

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“…However, they were able to regulate the accumulation of immune cells (i.e., T-cells) as well as the biosynthesis of cytokines (i.e., TNF-α, IL-1β, IL-2, IL-4, IL-10, and INF-γ) in immunocompetent BALB/c mice [102,103]. Further evidence is supported by experimental animal models fed EGCG and naringenin-enriched diet showing accumulation and activation of T-cells in response to tumour-promoting stimuli [104,105].…”

Section: Evidence Of the Chemopreventive Potential Of Phenolic Compoumentioning

confidence: 91%

Dietary Phenolics against Breast Cancer. A Critical Evidence-Based Review and Future Perspectives

Ávila‐Gálvez

Giménez‐Bastida

Espı́n

et al. 2020

IJMS

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Breast cancer (BC) is the most common malignancy and the leading cause of cancer-related death in adult women worldwide. Over 85% of BC cases are non-hereditary, caused by modifiable extrinsic factors related to lifestyle, including dietary habits, which play a crucial role in cancer prevention. Although many epidemiological and observational studies have inversely correlated the fruit and vegetable consumption with the BC incidence, the involvement of their phenolic content in this correlation remains contradictory. During decades, wrong approaches that did not consider the bioavailability, metabolism, and breast tissue distribution of dietary phenolics persist behind the large currently existing gap between preclinical and clinical research. In the present review, we provide comprehensive preclinical and clinical evidence according to physiologically relevant in vitro and in vivo studies. Some dietary phenolics such as resveratrol (RSV), quercetin, isoflavones, epigallocatechin gallate (EGCG), lignans, and curcumin are gaining attention for their chemopreventive properties in preclinical research. However, the clinical evidence of dietary phenolics as BC chemopreventive compounds is still inconclusive. Therefore, the only way to validate promising preclinical results is to conduct clinical trials in BC patients. In this regard, future perspectives on dietary phenolics and BC research are also critically discussed.

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Section: Evidence Of the Chemopreventive Potential Of Phenolic Compoumentioning

confidence: 91%

Dietary Phenolics against Breast Cancer. A Critical Evidence-Based Review and Future Perspectives

Ávila‐Gálvez

Giménez‐Bastida

Espı́n

et al. 2020

IJMS

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“…Thus far, only few studies mentioned COL8A1 in breast cancer. COL8A1 was one of the key genes restored by epigallocatechin-3-gallate in a murine breast cancer model [41]. COL8A1 proved downregulated in both BRIP1-knockdown breast cancer cells and MCF10A CDH1-/-non-cancer breast cells [42,43].…”

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confidence: 97%

Clinical value and potential mechanisms of COL8A1 upregulation in breast cancer: a comprehensive analysis

Wei

Zeng

et al. 2020

Cancer Cell Int

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Background: The situation faced by breast cancer patients, especially those with triple-negative breast cancer, is still grave. More effective therapeutic targets are needed to optimize the clinical management of breast cancer. Although collagen type VIII alpha 1 chain (COL8A1) has been shown to be downregulated in BRIP1-knockdown breast cancer cells, its clinical role in breast cancer remains unknown. Methods: Gene microarrays and mRNA sequencing data were downloaded and integrated into larger matrices based on various platforms. Therefore, this is a multi-centered study, which contains 5048 breast cancer patients and 1161 controls. COL8A1 mRNA expression in breast cancer was compared between molecular subtypes. In-house immunohistochemistry staining was used to evaluate the protein expression of COL8A1 in breast cancer. A diagnostic test was performed to assess its clinical value. Furthermore, based on differentially expressed genes (DEGs) and coexpressed genes (CEGs) positively related to COL8A1, functional enrichment analyses were performed to explore the biological function and potential molecular mechanisms of COL8A1 underlying breast cancer. Results: COL8A1 expression was higher in breast cancer patients than in control samples (standardized mean difference = 0.79; 95% confidence interval [CI] 0.55-1.03). Elevated expression was detected in various molecular subtypes of breast cancer. An area under a summary receiver operating characteristic curve of 0.80 (95% CI 0.76-0.83) with sensitivity of 0.77 (95% CI 0.69-0.83) and specificity of 0.70 (95% CI 0.61-0.78) showed moderate capacity of COL8A1 in distinguishing breast cancer patients from control samples. Worse overall survival was found in the higher than in the lower COL8A1 expression groups. Intersected DEGs and CEGs positively related to COL8A1 were significantly clustered in the proteoglycans in cancer and ECM-receptor interaction pathways. Conclusions: Elevated COL8A1 may promote the migration of breast cancer by mediating the ECM-receptor interaction and synergistically interplaying with DEGs and its positively related CEGs independently of molecular subtypes. Several genes clustered in the proteoglycans in cancer pathway are potential targets for developing effective agents for triple-negative breast cancer.

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“…Meanwhile, we also established another TNBC model by in situ inoculation of human TNBC cell line (MDA-MB-231) into BALB/c nude mice (Shi et al, 2019;Kachamakova-Trojanowska et al, 2020;Xu et al, 2020). As shown in Figure 6C, RBF also showed significant antitumor activity in this tumor model, and the tumor volume was 146.77 ± 37.5 mm 3 much smaller than that in the control group (244.31 ± 62.9 mm 3 ).…”

Section: Resibufogenin Inhibited Tumor Angiogenesis and Growth In 4t1 And Mda-mb-231 Orthotopic Mouse Modelsmentioning

confidence: 92%

Resibufogenin Suppresses Triple-Negative Breast Cancer Angiogenesis by Blocking VEGFR2-Mediated Signaling Pathway

Yang

Jiang

et al. 2021

Front. Pharmacol.

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Resibufogenin (RBF), an active compound from Bufo bufonis, has been used for the treatment of multiple malignant cancers, including pancreatic cancer, colorectal cancer, and breast cancer. However, whether RBF could exert its antitumor effect by inhibiting angiogenesis remains unknown. Here, we aimed to explore the antiangiogenic activity of RBF and its underlying mechanism on human umbilical vein endothelial cell (HUVEC), and the therapeutic efficacy with regard to antiangiogenesis in vivo using two triple-negative breast cancer (TNBC) models. Our results demonstrated that RBF can inhibit the proliferation, migration, and tube formation of HUVECs in a dose-dependent manner. Spheroid sprouts were thinner and shorter after RBF treatment in vitro 3D spheroid sprouting assay. RBF also significantly suppressed VEGF-mediated vascular network formation in vivo Matrigel plug assay. In addition, Western blot analysis was used to reveal that RBF inhibited the phosphorylation of VEGFR2 and its downstream protein kinases FAK and Src in endothelial cells (ECs). Molecular docking simulations showed that RBF affected the phosphorylation of VEGFR2 by competitively binding to the ATP-bound VEGFR2 kinase domain, thus preventing ATP from providing phosphate groups. Finally, we found that RBF exhibited promising antitumor effect through antiangiogenesis in vivo without obvious toxicity. The present study first revealed the high antiangiogenic activity and the underlying molecular basis of RBF, suggesting that RBF could be a potential antiangiogenic agent for angiogenesis-related diseases.

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Green Tea Polyphenol EGCG Attenuates MDSCs-mediated Immunosuppression through Canonical and Non-Canonical Pathways in a 4T1 Murine Breast Cancer Model

Cited by 53 publications

References 57 publications

Dietary Phenolics against Breast Cancer. A Critical Evidence-Based Review and Future Perspectives

Dietary Phenolics against Breast Cancer. A Critical Evidence-Based Review and Future Perspectives

Clinical value and potential mechanisms of COL8A1 upregulation in breast cancer: a comprehensive analysis

Resibufogenin Suppresses Triple-Negative Breast Cancer Angiogenesis by Blocking VEGFR2-Mediated Signaling Pathway

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