Tocotrienol-adjuvanted dendritic cells inhibit tumor growth and metastasis: a murine model of breast cancer

PLoS One. 2013 Sep 19;8(9):e74753. doi: 10.1371/journal.pone.0074753. eCollection 2013.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • B7-1 Antigen / genetics
  • B7-1 Antigen / metabolism
  • B7-2 Antigen / genetics
  • B7-2 Antigen / metabolism
  • Biomarkers / metabolism
  • Breast Neoplasms / genetics
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / therapy
  • CD40 Antigens / genetics
  • CD40 Antigens / metabolism
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Disease Models, Animal
  • Female
  • Gene Expression
  • Humans
  • Immunoglobulins / genetics
  • Immunoglobulins / metabolism
  • Interferon-gamma / biosynthesis
  • Interleukin-12 / biosynthesis
  • Lung Neoplasms / pathology
  • Lung Neoplasms / secondary
  • Mammary Neoplasms, Experimental
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mice
  • Neoplasm Grading
  • Neoplasm Metastasis
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism
  • Tocotrienols / administration & dosage*
  • Tumor Burden / drug effects

Substances

  • Adjuvants, Immunologic
  • Antigens, CD
  • Antineoplastic Agents, Phytogenic
  • B7-1 Antigen
  • B7-2 Antigen
  • Biomarkers
  • CD40 Antigens
  • CD83 antigen
  • Immunoglobulins
  • Membrane Glycoproteins
  • Tocotrienols
  • Interleukin-12
  • Interferon-gamma

Grant support

This study was supported by a research grant from the International Medical University (IMU) and the Malaysian Palm Oil Board (MPOB). This work is part of the work that the first author did for her PhD, which is supported by the MPOB and IMU. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.