Immunomodulatory/inflammatory effects of geopropolis produced by Melipona fasciculata Smith in combination with doxorubicin on THP-1 cells

J Pharm Pharmacol. 2016 Dec;68(12):1551-1558. doi: 10.1111/jphp.12649. Epub 2016 Oct 17.

Abstract

Objectives: Geopropolis (GEO) in combination with doxorubicin (DOX) reduced HEp-2 cells viability compared to GEO and DOX alone. A possible effect of this combination on the innate immunity could take place, and its effects were analysed on THP-1 cell - a human leukaemia monocytic cell line used as a model to study monocyte activity and macrophage activity, assessing cell viability, expression of cell markers and cytokine production.

Methods: THP-1 cells were incubated with GEO, DOX and their combination. Cell viability was assessed by MTT assay, cell markers expression by flow cytometry and cytokine production by ELISA.

Key findings: GEO + DOX did not affect cell viability. GEO alone or in combination increased TLR-4 and CD80 but not HLA-DR and TLR-2 expression. GEO stimulated TNF-α production while DOX alone or in combination did not affect it. GEO alone or in combination inhibited IL-6 production.

Conclusions: GEO exerted a pro-inflammatory profile by increasing TLR-4 and CD80 expression and TNF-α production, favouring the activation of the immune/inflammatory response. GEO + DOX did not affect cell viability and presented an immunomodulatory action. Lower concentrations of DOX combined to GEO could be used in cancer patients, avoiding side effects and benefiting from the biological properties of GEO.

Keywords: THP-1 cells; cell markers; chemotherapeutic agent; geopropolis; immunomodulation.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / toxicity
  • B7-1 Antigen
  • Bees*
  • Biomarkers / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Doxorubicin / pharmacology*
  • Doxorubicin / toxicity
  • HLA-DR Antigens / metabolism
  • Humans
  • Inflammation / chemically induced
  • Inflammation / immunology
  • Inflammation / metabolism
  • Inflammation / prevention & control*
  • Inflammation Mediators / immunology
  • Inflammation Mediators / metabolism*
  • Interleukin-6 / metabolism
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Macrophages / metabolism
  • Monocytes / drug effects*
  • Monocytes / immunology
  • Monocytes / metabolism
  • Propolis / pharmacology*
  • Propolis / toxicity
  • Time Factors
  • Toll-Like Receptor 2 / metabolism
  • Toll-Like Receptor 4 / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • B7-1 Antigen
  • Biomarkers
  • HLA-DR Antigens
  • IL6 protein, human
  • Inflammation Mediators
  • Interleukin-6
  • TLR2 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • Doxorubicin
  • Propolis