Zymosan attenuates melanoma growth progression, increases splenocyte proliferation and induces TLR-2/4 and TNF-α expression in mice

  • J Inflamm (Lond). 2018 Mar 22:15:5. doi: 10.1186/s12950-018-0182-y.
Mehdi Taghavi  1 ,  Esmaeil Mortaz  2  3  4 ,  Alireza Khosravi  1 ,  Ghasem Vahedi  1 ,  Gert Folkerts  3 ,  Mohammad Varahram  5 ,  Mehdi Kazempour-Dizaji  5 ,  Johan Garssen  3  6 ,  Ian M Adcock  7
Affiliations
  • 1. 1Mycology Research Center, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
  • 2. 2Department of Immunology, Faculty of Medicine, ShahidBeheshti University of Medical Sciences, Tehran, Iran.
  • 3. 3Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Sciences, Utrecht University, Utrecht, the Netherlands.
  • 4. 4Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • 5. 5Mycobacteriology Research Center (MRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • 6. 6Nutricia Research Centre for Specialized Nutrition, Utrecht, Netherlands.
  • 7. 7Airways Disease Section, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, UK.
PMID: 29588627 DOI: 10.1186/s12950-018-0182-y
Abstract

Background: Melanoma is one of the most common types of skin malignancies. Since current therapies are suboptimal, considerable interest has focused on novel natural-based treatments. Toll-like receptors (TLRs) play an important role in evoking innate immunity against Cancer cells. Zymosan, a known TLR-2 agonist, is a glucan derived from yeast cell walls with promising immunomodulatory effects. The aim of this study was to evaluate whether Saccharomyces cerevisiae-derived zymosan-modulated skin melanoma progression by regulation of TLR-2 and TLR-4 expression in peritoneal macrophages and serum TNF-α level.

Methods: Male C57BL/6 mice were divided into four groups: i) zymosan-treated (Z), ii) Melanoma-bearing mice (M), iii) Melanoma-bearing mice treated with zymosan (ZM) and iv) a healthy control group (negative control). 15 days after melanoma induction, mice were injected i.p. with zymosan (10 μg) daily for 4 consecutive days. Mice were CO2-euthanized and serum TNF-α level, TLR-2 and TLR-4 expression in peritoneal macrophages and tumor growth measured. Splenocytes were treated ex-vivo with zymosan to determine viability and proliferation.

Results: Tumor weight significantly decreased following therapeutic dosing with zymosan (P < 0.05). This was associated with zymosan-induced upregulation of TLR-2, TLR-4 and TNF-α mRNA in peritoneal macrophages and enhanced serum TNF-α levels (P < 0.05). Splenocyte number and viability were increased in a concentration-dependent manner by zymosan.

Conclusions: Our study suggests that zymosan-induced upregulation of TLR-2, TLR-4 and TNF-α gene expression and of TNF-α release; together with increased level of lymphocyte proliferation may play a role in the inhibition of melanoma progression.

Keywords
TLR-2; TLR-4; TNF-α; Zymosan.
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