scholarly journals Polyphenol-Rich Muscadine Grape Extract Reduces Triple Negative Breast Cancer Metastasis in Mice with Changes in the Gut Microbiome

2021 ◽  
Author(s):  
Marianne Collard ◽  
Nataleigh N Austin ◽  
Heather Brown-Harding ◽  
Brian Westwood ◽  
E Ann Tallant ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Cancer Metastasis ◽  
Triple Negative ◽  
Breast Cancer Metastasis ◽  
Metastatic Progression ◽  
Microbial Composition ◽  
Cytoskeletal Organization ◽  
Grape Extract ◽  
Muscadine Grape

Abstract Background Triple negative breast cancer (TNBC) has a high propensity to metastasize and no treatments are available to slow or prevent metastatic progression. The goal of this study is to determine whether a proprietary high-polyphenol content muscadine grape extract (MGE) inhibits TNBC metastasis. Methods 4T1 TNBC cells were injected into the mammary fat pad of 6-week-old female Balb/c mice. After 2 weeks, tumors were surgically removed and mice were placed into a control (n=8) or treatment group that received 0.1 mg/mL total phenolics MGE in the drinking water (n=8) for 4 weeks. Immunohistochemistry (Ki67, α-SMA) and hemotoxylin and eosin staining were used to quantify metastases. Gut microbial composition was determined by 16S rRNA sequencing and short chain fatty acids (SCFAs) were detected by gas chromatography. MDA-MB-231, BT-549 and 4T1 TNBC cell motility and cytoskeletal organization was assessed in vitr o by scratch wound migration and confocal microscopy, respectively. Data were evaluated by student’s t -test. Results MGE reduced metastatic proliferation in mouse lungs (33.3%) and livers (58.3%) and decreased the number (51.1%) and size (17.4%) of liver metastases, resulting in a 55.7% reduction in metastatic tumor burden ( P < 0.01). Serum IL-6 was reduced 99.6% in MGE-treated mice ( P = 0.06). MGE attenuated migration, altered cytoskeletal organization, and reduced RHAMM expression in TNBC cells ( P < 0.05). The gut microbiota, a mediator of polyphenolic bioactivities, was altered significantly in MGE-treated mice; MGE increased the alpha diversity (7.14%), Firmicutes/Bacteroidetes ratio (2-fold), relative abundance of butyrate-producing genera, and butyrate (3-fold) ( P < 0.05). Butyrate inhibited 4T1 cell proliferation and migration, suggesting butyrate contributes to MGE’s anti-metastatic activities ( P < 0.05). Conclusion Our results indicate that MGE may be an effective adjuvant therapy to reduce TNBC metastatic progression.

scholarly journals CPSF4 promotes triple negative breast cancer metastasis by upregulating MDM4

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Kaping Lee ◽  
Qiufan Zheng ◽  
Qianyi Lu ◽  
Fei Xu ◽  
Ge Qin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Cancer Metastasis ◽  
Triple Negative ◽  
Breast Cancer Metastasis

scholarly journals DCAF13 promotes triple-negative breast cancer metastasis by mediating DTX3 mRNA degradation

Cell Cycle ◽  
2020 ◽  
Vol 19 (24) ◽  
pp. 3622-3631
Author(s):  
Jiazhe Liu ◽  
Hongchang Li ◽  
Anwei Mao ◽  
Jingfeng Lu ◽  
Weiyan Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Cancer Metastasis ◽  
Triple Negative ◽  
Mrna Degradation ◽  
Breast Cancer Metastasis

scholarly journals A Polyphenol Rich Muscadine Grape Extract Reduces Triple Negative Breast Cancer Cell Migration in Association with Changes in Cell Morphology and Motility-Related Proteins

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 325-325
Author(s):  
Patricia Gallagher ◽  
Marianne Collard ◽  
Heather Brown-Harding ◽  
Elisabeth Tallant
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Confocal Microscopy ◽  
Triple Negative Breast Cancer ◽  
Cell Shape ◽  
Molecular Mechanisms ◽  
Triple Negative ◽  
Dependent Manner ◽  
Grape Extract ◽  
Muscadine Grape

Abstract Objectives Triple negative breast cancer (TNBC) is a subtype of breast cancer characterized by the lack of estrogen receptors, progesterone receptors and over-expression of the human epidermal growth factor receptor 2, limiting targeted treatment.  TNBC disproportionally affects ethnic minorities and younger women and has a high propensity to metastasize, often within 5 years of diagnosis, making it one of the most aggressive breast cancer subtypes.  We showed that treatment with a proprietary muscadine grape extract (MGE) reduced the growth and metastasis of TNBC in mice.  Muscadine grapes (V. Rotundifolia) are rich in polyphenols and extracts produced from muscadine grape seed and skin are marketed as nutraceuticals for their anti-oxidant, anti-inflammatory, and anti-cancer properties.  The goal of these studies was to determine the molecular mechanisms for the reduction in metastatic growth by MGE. Methods A proprietary extract was prepared from muscadine grape seeds and skins.  Migration of MDA-MB-231 and BT-549 cells was measured by a scratch wound assay, cell shape was visualized by confocal microscopy and mRNA/proteins that participate in cell migration/motility were measured by RT-PCR and western blot hybridization. Results The extract reduced the migration of MDA-MB-231 and BT-549 TNBC cells in a dose-dependent manner.  The reduction in cell migration was associated with MGE-induced alterations in cell shape and actin filament organization, visualized by confocal microscopy.  The extract caused an apparent loss of cell polarization in MDA-MB-231 cells and a reduction in the presence of filopodia in BT-549 cells.  The MGE-induced reduction in migration and alterations in cell shape and polarization were associated with a decrease in Rho kinase ROCK1/2 mRNA and protein as well as both the mRNA and protein expression of RHAMM, a protein that is implicated in both cell motility and breast cancer progression. Conclusions These results demonstrate that a proprietary MGE reduces TNBC cell migration, in association with changes in cell shape and cytoskeleton as well as proteins that regulate migration and motility, suggesting that treatment of TNBC patients with MGE may slow or prevent metastatic progression. Funding Sources Chronic Disease Research Fund.

scholarly journals MicroRNA-200b targets protein kinase Cα and suppresses triple-negative breast cancer metastasis

2014 ◽  
Vol 35 (10) ◽  
pp. 2254-2263 ◽  
Author(s):  
Brock Humphries ◽  
Zhishan Wang ◽  
Aaron L. Oom ◽  
Theresa Fisher ◽  
Dongfeng Tan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Kinase ◽  
Triple Negative Breast Cancer ◽  
Cancer Metastasis ◽  
Triple Negative ◽  
Breast Cancer Metastasis ◽  
Protein Kinase Cα

scholarly journals Sanguisorba officinalis L. Suppresses Triple-Negative Breast Cancer Metastasis by Inhibiting Late-Phase Autophagy via Hif-1α/Caveolin-1 Signaling

2020 ◽  
Vol 11 ◽  
Author(s):  
Neng Wang ◽  
Gulizeba Muhetaer ◽  
Xiaotong Zhang ◽  
Bowen Yang ◽  
Caiwei Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Triple Negative ◽  
Late Phase ◽  
Breast Cancer Metastasis ◽  
Chinese Herbs ◽  
Caveolin 1 ◽  
Sanguisorba Officinalis

Sanguisorba officinalis L. (SA) is a common herb for cancer treatment in the clinic, particularly during the consolidation phase to prevent occurrence or metastasis. Nevertheless, there are limited studies reporting the molecular mechanisms about its anti-metastatic function. It is well demonstrated that autophagy is one of the critical mechanisms accounting for metastasis and anti-cancer pharmacological actions of Chinese herbs. On the threshold, the regulatory effects and molecular mechanisms of SA in suppressing autophagy-related breast cancer metastasis were investigated in this study. In vitro findings demonstrated that SA potently suppressed the proliferation, colony formations well as metastasis process in triple-negative breast cancer. Network and biological analyses predicted that SA mainly targeted caveolin-1 (Cav-1) to induce anti-metastatic effects, and one of the core mechanisms was via regulation of autophagy. Further experiments—including western blotting, transmission electron microscopy, GFP-mRFP-LC3 immunofluorescence, and lysosomal-activity detection—validated SA as a potent late-stage autophagic inhibitor by increasing microtubule-associated light chain 3-II (LC3-II) conversion, decreasing acidic vesicular-organelle formation, and inducing lysosomal dysfunction even under conditions of either starvation or hypoxia. Furthermore, the anti-autophagic and anti-metastatic activity of SA was Cav-1-dependent. Specifically, Cav-1 knockdown significantly facilitated SA-mediated inhibition of autophagy and metastasis. Furthermore, hypoxia inducible factor-1α (Hif-1α) overexpression attenuated the SA-induced inhibitory activities on Cav-1, autophagy, and metastasis, indicating that SA may have inhibited autophagy-related metastasis via Hif-1α/Cav-1 signaling. In both mouse breast cancer xenograft and zebrafish xenotransplantation models, SA inhibited breast cancer growth and inhibited late-phase autophagy in vivo, which was accompanied by suppression of Hif-1α/Cav-1 signaling and the epithelial-mesenchymal transition. Overall, our findings not only indicate that SA acts as a novel late-phase autophagic inhibitor with anti-metastatic activities in triple-negative breast cancer, but also highlight Cav-1 as a regulator in controlling late-phase autophagic activity.

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