Tocotrienol-Adjuvanted Dendritic Cells Inhibit Tumor Growth and Metastasis: A Murine Model of Breast Cancer

Abstract

Tocotrienol-rich fraction (TRF) from palm oil is reported to possess anti-cancer and immune-enhancing effects. In this study, TRF supplementation was used as an adjuvant to enhance the anti-cancer effects of dendritic cells (DC)-based cancer vaccine in a syngeneic mouse model of breast cancer. Female BALB/c mice were inoculated with 4T1 cells in mammary pad to induce tumor. When the tumor was palpable, the mice in the experimental groups were injected subcutaneously with DC-pulsed with tumor lysate (TL) from 4T1 cells (DC+TL) once a week for three weeks and fed daily with 1 mg TRF or vehicle. Control mice received unpulsed DC and were fed with vehicle. The combined therapy of using DC+TL injections and TRF supplementation (DC+TL+TRF) inhibited (p<0.05) tumor growth and metastasis. Splenocytes from the DC+TL+TRF group cultured with mitomycin-C (MMC)-treated 4T1 cells produced higher (p<0.05) levels of IFN-γ and IL-12. The cytotoxic T-lymphocyte (CTL) assay also showed enhanced tumor-specific killing (p<0.05) by CD8+ T-lymphocytes isolated from mice in the DC+TL+TRF group. This study shows that TRF has the potential to be used as an adjuvant to enhance effectiveness of DC-based vaccines.

Bioactive Compounds: Natural Defense Against Cancer?

“…Tocotrienol isoforms inhibited proliferation of human breast cancer cells in the following order: αT3 < TRF < γT3 < δT3 [137]. In addition, daily supplementation of 1 mg of TRF was reported to inhibit tumor growth in a syngeneic murine model of breast cancer [31,124,137]. A similar observation was also reported in a xenograft athymic mouse model of breast cancer where a significant delay in the onset of breast cancer in mice fed with 1 mg TRF was observed [138].…”

“…TRF contains three main isoforms of tocotrienol, which are αT3 (29%), γT3 (28%) and δT3 (14%) isomers [119]. Tocotrienols are reported to possess anti-thrombotic [120], antioxidant [121], neuroprotective [122] and cardio-protective [123] activities as well as immune modulatory [124,125] properties. Both cell-based and experimental model studies have suggested that tocotrienols also possess anti-tumor properties as these compounds can inhibit proliferation of many cancer cell lines including prostate [126], breast [127], skin [128], colon [129], stomach [130], pancreatic [131], liver [132] and lung [133] cancers.…”

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

“…The bone marrow (BM) was harvested under aseptic conditions. The tibia and femur bones were obtained from euthanized BALB/c mice and the BM cells were obtained by flushing the cut tibia and femur bones with complete medium using a 22 cc needle syringe as described previously [19,24]. Complete medium (CM) consisted of RPMI 1640 media with 10% fetal bovine serum (FBS, heat-inactivated), 1% glutamine, and 1% penicillin-streptomycin (PenStrep) added.…”

“…A week after the last DC injection, the mice in all five study groups received a single injection of 4T1 cells (50 µL of 4T1 cells in phosphate-buffered saline (PBS)) into their mammary fat pad. As reported previously, the tumor was usually palpable on day 14 [21,24]. Tumor growth was monitored once a week by measuring the size of the primary tumor using a digital caliper.…”

“…Tocotrienols have been the focus of increasing research interest in the last 5-10 years as a unique nutritional compound. The scientific evidence to date has shown that in addition to being powerful biological antioxidants, tocotrienols can reduce cholesterol levels in people with hypercholesterolemia, may slow down the progression of atherosclerosis, and possess anti-cancer properties [22][23][24]. We have previously reported that vaccinating mice with DC pulsed with tumor lysate from 4T1 cells (DC + TL) and daily supplementation with 1 mg TRF inhibited tumor growth and produced a tumor-specific immune response [21,24].…”