Self-assembled betulinic acid augments immunomodulatory activity associates with IgG response

Biomed Pharmacother. 2015 Oct:75:205-17. doi: 10.1016/j.biopha.2015.07.033. Epub 2015 Sep 1.

Abstract

Studies relating to the adjuvanic role of self assembly, nanosized betulinic acid (SA-BA) are relatively limited. The concept of immunostimulatory activity of SA-BA is based on the activation of immune system against cancer antigen. This study showed that SA-BA, a pentacyclic triterpene isolated from the bark of the Ziziphus jujube tree, elevated the immunological functions of cancer antigen in anticancer immunotherapy. We found that, SA-BA pulsed human macrophages secreted elevated level of pro-inflammatory cytokines with an increased CD4(+) cell population. Pulse macrophages were also significantly arrested the KG-1A and K562 cell growth in vitro setup at 1:10 ratio for 48h. The use of TNF-α inhibitors confirmed the association between SA-BA with TNF-α function. SA-BA pulsed macrophages displayed substantial T cell allostimulatory capacity and promoted the generation of cytotoxic T lymphocytes (CTLs). The adjuvanticity of SA-BA was proved by the generation of in vivo IgG response. Collectively, these findings will enrich the biomedical applications of SA-BA as a potent immune stimulating agent. Moreover, the macrophage stimulating efficacy of SA-BA might be an effective way in the cancer immunotherapy.

Keywords: Cytotoxicity; IgG; SA-BA; T cells; TNF- α.

MeSH terms

  • Adjuvants, Immunologic / chemistry
  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Betulinic Acid
  • Cell Communication / drug effects
  • Cell Cycle Checkpoints / drug effects
  • Chemistry, Pharmaceutical
  • Coculture Techniques
  • Cytokines / metabolism
  • Dose-Response Relationship, Drug
  • Humans
  • Immunoglobulin G / blood*
  • Inflammation Mediators / metabolism
  • K562 Cells
  • Lymphocyte Activation / drug effects
  • Lymphoma / drug therapy*
  • Lymphoma / immunology
  • Lymphoma / metabolism
  • Lymphoma / pathology
  • Macrophage Activation / drug effects
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Macrophages / metabolism
  • Male
  • Mice
  • Nanoparticles
  • Pentacyclic Triterpenes
  • T-Lymphocytes, Cytotoxic / drug effects*
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism
  • Time Factors
  • Triterpenes / chemistry
  • Triterpenes / pharmacology*
  • Tumor Burden / drug effects

Substances

  • Adjuvants, Immunologic
  • Antineoplastic Agents, Phytogenic
  • Cytokines
  • Immunoglobulin G
  • Inflammation Mediators
  • Pentacyclic Triterpenes
  • Triterpenes
  • Betulinic Acid