PALM GAMMA-TOCOTRIENOL SUPPLEMENTATION SUPPRESS TUMOUR GROWTH AND METASTASIS IN A SYNGENEIC MOUSE MODEL OF BREAST CANCER

Nutrition can modulate host immune responses as well as promote anticancer effects. In this study, two nutritional supplements, namely gamma-tocotrienol (γT3) and Spirulina, were evaluated for their immune-enhancing and anticancer effects in a syngeneic mouse model of breast cancer (BC). Five-week-old female BALB/c mice were fed Spirulina, γT3, or a combination of Spirulina and γT3 (Spirulina + γT3) for 56 days. The mice were inoculated with 4T1 cells into their mammary fat pad on day 28 to induce BC. The animals were culled on day 56 for various analyses. A significant reduction (p < 0.05) in tumor volume was only observed on day 37 and 49 in animals fed with the combination of γT3 + Spirulina. There was a marked increase (p < 0.05) of CD4/CD127+ T-cells and decrease (p < 0.05) of T-regulatory cells in peripheral blood from mice fed with either γT3 or Spirulina. The breast tissue of the combined group showed abundant areas of necrosis, but did not prevent metastasis to the liver. Although there was a significant increase (p < 0.05) of MIG-6 and Cadherin 13 expression in tumors from γT3-fed animals, there were no significant (p > 0.05) differences in the expression of MIG-6, Cadherin 13, BIRC5, and Serpine1 upon combined feeding. This showed that combined γT3 + Spirulina treatment did not show any synergistic anticancer effects in this study model.

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Gamma-tocotrienol modifies methylation of HOXA10, IRF4 and RORα genes in CD4+ T-lymphocytes: Evidence from a syngeneic mouse model of breast cancer

Current Research in Immunology ◽

10.1016/j.crimmu.2021.10.001 ◽

2021 ◽

Vol 2 ◽

pp. 169-174

Author(s):

Ammu K. Radhakrishnan ◽

Jeya Seela Anandha Rao ◽

Shonia Subramaniam ◽

Premdass Ramdas

Keyword(s):

Breast Cancer ◽

T Lymphocytes ◽

Mouse Model ◽

Syngeneic Mouse ◽

Syngeneic Mouse Model ◽

Gamma Tocotrienol

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TAMI-06. TUMOR CELL-DERIVED CYTOKINE EXPRESSION CHANGES ASSOCIATED WITH BRAIN METASTASIS IN A SYNGENEIC MOUSE MODEL OF BREAST CANCER

Neuro-Oncology ◽

10.1093/neuonc/noab196.790 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi199-vi199

Author(s):

Ramin Morshed ◽

Alexander Haddad ◽

Saket Jain ◽

Sabraj Gill ◽

Jordan Spatz ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Mouse Model ◽

Tumor Cell ◽

Expression Analysis ◽

Gene Expression Analysis ◽

Cytokine Expression ◽

Metastatic Dissemination ◽

Syngeneic Mouse ◽

Syngeneic Mouse Model

Abstract Breast cancer is the most common malignancy in women in the United States, and brain metastases occur in almost a third of patients with metastatic dissemination. Immunoediting is a critical component of metastatic tumor cell elimination, and tumor clones that develop immune-escape mechanisms are associated with progression and metastatic dissemination. We hypothesized that breast cancer brain metastatic cells harbor immunomodulatory cytokine expression changes that promote an immunosuppressive environment to avoid immune cell-mediated elimination. To study this, a syngeneic mouse model of metastatic breast cancer was used. A brain metastatic line derived from the 4T1 breast cancer parental cell line was created by serially selecting brain metastatic populations of cells after intracardiac injection (4T1 BrM). A gene-expression analysis using an 800-gene cancer immunology-specific microarray panel was performed comparing the 4T1 parental and 4T1 BrM lines. 4T1 BrM cells demonstrate gene expression changes promoting immunosuppression including significant upregulation of IL18 and Lgals9 (Galectin-9) and downregulation of CD40, IL2rg, CCL2, and EOMES. When compared to 4T1 parental lines, the 4T1 BrM line demonstrated decreased expression of CCL2 and increased expression of GM-CSF on a cytokine array, corresponding to results obtained from gene expression analysis. These results suggest tumor-intrinsic cytokine expression changes that may mediate an immunosuppressive environment.

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Osteolytic Breast Cancer Causes Skeletal Muscle Weakness in an Immunocompetent Syngeneic Mouse Model

Frontiers in Endocrinology ◽

10.3389/fendo.2017.00358 ◽

2017 ◽

Vol 8 ◽

Cited By ~ 9

Author(s):

Jenna N. Regan ◽

Carter Mikesell ◽

Steven Reiken ◽

Haifang Xu ◽

Andrew R. Marks ◽

...

Keyword(s):

Breast Cancer ◽

Skeletal Muscle ◽

Mouse Model ◽

Muscle Weakness ◽

Syngeneic Mouse ◽

Syngeneic Mouse Model ◽

Skeletal Muscle Weakness

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Multimodality cellular and molecular imaging of concomitant tumour enhancement in a syngeneic mouse model of breast cancer metastasis

Scientific Reports ◽

10.1038/s41598-018-27208-4 ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 1

Author(s):

Katie M. Parkins ◽

Veronica P. Dubois ◽

Amanda M. Hamilton ◽

Ashley V. Makela ◽

John A. Ronald ◽

...

Keyword(s):

Breast Cancer ◽

Molecular Imaging ◽

Mouse Model ◽

Cancer Metastasis ◽

Breast Cancer Metastasis ◽

Syngeneic Mouse ◽

Syngeneic Mouse Model

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Macrophages promote tumour growth and liver metastasis in an orthotopic syngeneic mouse model of colon cancer

International Journal of Colorectal Disease ◽

10.1007/s00384-013-1703-z ◽

2013 ◽

Vol 28 (10) ◽

pp. 1337-1349 ◽

Cited By ~ 29

Author(s):

J. Kruse ◽

W. von Bernstorff ◽

K. Evert ◽

N. Albers ◽

S. Hadlich ◽

...

Keyword(s):

Colon Cancer ◽

Liver Metastasis ◽

Mouse Model ◽

Tumour Growth ◽

Syngeneic Mouse ◽

Syngeneic Mouse Model

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Reduced infiltration of T-regulatory cells in tumours from mice fed daily with gamma-tocotrienol supplementation

10.22541/au.162186986.63086815/v1 ◽

2021 ◽

Author(s):

Shonia Subramaniam ◽

Jeya Seela Anandha Rao ◽

Premdass Ramdas ◽

Mei Han Ng ◽

Methil Kannan Kutty ◽

...

Keyword(s):

Gene Expression ◽

T Cells ◽

Mouse Model ◽

Treg Cells ◽

Interleukin 12 ◽

Syngeneic Mouse ◽

Expression Studies ◽

Syngeneic Mouse Model ◽

Gene Expression Studies ◽

Gamma Tocotrienol

Gamma-tocotrienol (γT3) is an analogue of vitamin E with beneficial effects on the immune system, including immune-modulatory properties. This study reports the immune-modulatory effects of daily supplementation of γT3 on host T-helper (Th) and T-regulatory (Treg) populations in a syngeneic mouse model of breast cancer. Female BALB/c mice were fed with either γT3 or vehicle (soy oil) for 2-weeks via oral gavage before they were inoculated with syngeneic 4T1 mouse mammary cancer cells (4T1 cells). Supplementation continued until the mice were sacrificed. Mice (n=6) were sacrificed at specified time-points for various analysis (blood leucocyte, cytokine production, and immunohistochemistry). Tumour volume was measured once every seven days. Gene expression studies were carried out on tumour-specific T-lymphocytes isolated from splenic cultures. Supplementation with γT3 increased CD4+ (p<0.05), CD8+ (p<0.05) T-cells and natural killer cells (p<0.05) but suppressed Treg cells (p<0.05) in peripheral blood when compared to animals fed with the vehicle. Higher interferon-gamma (IFN) and lower transforming growth factor-beta (TGF-) levels were noted in the T3 fed mice. Immunohistochemistry findings revealed higher infiltration of CD4+ cells, increased expression of interleukin-12 receptor-beta-2 (IL-122R), interleukin-24 (IL-24) and reduced expression of cells that express the forkhead box P3 (FoxP3) in tumours from the T3 fed animals. Gene expression studies showed the downregulation of seven prominent genes in splenic CD4+ T-cells isolated from γT3-fed mice. Supplementation with γT3 from palm oil-induced T-cell dependent cell-mediated immune responses and suppressed Treg cells in the tumour microenvironment in a syngeneic mouse model of BC.

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