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

Abstract

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.

Palm Gamma-Tocotrienol Supplementation Suppress Tumour Growth and Metastasis in a Syngeneic Mouse Model of Breast Cancer

“…Hence, short term feeding of γT3 once tumour is palpable, may be insufficient to prepare the host immune system to control the tumour. Previous studies that have looked at effects of TRF supplementation in tumourinduced mice vaccinated with dendritic cell (DC) vaccines before (Abdul Hafid and Radhakrishnan, 2019;Abdul Hafid et al, 2013;Hafid et al, 2010) showed enhanced immune function and tumour suppression. However, it should be noted that in both these studies, the animals were supplemented with TRF for a longer period, which may have been sufficient to regulate the host immune system to fight against cancer.…”

Tocotrienol-rich Fraction Modulated Genes Responsible for Inflammation in Lipopolysaccharide-stimulated RAW 264.7 Macrophages

“…Tocotrienol (T3), a major component of vitamin E from palm oil, has unique antioxidant and antiinflammatory properties [9], which are beneficial in inflammation-associated diseases [10]. Several studies have shown that T3 acts as a potent inducer of apoptosis in many cancer cells [11,12,13]; possess immune regulatory roles, which reduces the risk of respiratory infections and allergy [14,15]; confer protection against oxidative stress [16,17]as well as cardiovascular [15] and neurodegenerative [17] diseases. Therefore, this study aimed to evaluate how T3 cause anti-inflammatory responses using a cellbased inflammation model, i.e.…”

Elucidating the Role of the Satb1 Gene in Breast Cancer Carcinogenesis in the Presence or Absence of Tocotrienol-Rich Fraction: Evidence From a Syngeneic Mouse Model of Breast Cancer

“…Some of these approaches might help curb the alarming rise in BC cases. Tocotrienol rich-fraction (TRF) is a naturally occurring form of vitamin E, which has been reported to induce apoptosis in various cancer cells in cell-based and animal studies (Abdul-Hafid et al, 2019;Aggarwal et al, 2019).…”

“…Tocotrienols are considered more potent than tocopherols and are promising anticancer agents due to their potent effects against many cancers (Ling et al, 2012). Several cell-based and animal model studies have shown that palm TRF possessed antitumour properties in prostate, breast, skin, colon, stomach, pancreatic, liver and lung cancers through apoptosis, anti-angiogenesis, anti-proliferative and immunoregulation (Parveez et al, 2019;Abdul-Hafid et al, 2019;Aggarwal et al, 2019). Studies conducted by researchers showed that tocotrienols possessed several anticancer properties that made them superior to tocopherols (Ling et al, 2012;Wong et al, 2020).…”