Sorafenib induces autophagy and suppresses activation of human macrophage

Jiunn Chang Lin, Chien Liang Liu, Jie Jen Lee, Tsan Pai Liu, Wen Chin Ko, Yu Chuen Huang, Chih Hsiung Wu, Yu Jen Chen

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Background Sorafenib, a multi-kinase inhibitor approved for treatment of advanced renal cell carcinoma and other malignancies, has been shown as a modulator for dendritic cells. This study was designed to examine the effects of sorafenib on macrophages, the major ontogeny of innate immunity. Materials and methods Macrophages were derived from sorted CD14+ monocytes of human peripheral blood mononuclear cells. Cell viability and surface antigens were examined by trypan blue analysis. Autophagy was characterized by light microscopy and transmission electron microscopy for morphology, Western blotting for microtubule associated light chain protein 3B (LC-3B) I lipidation, and acridine orange staining for acidic component vacuoles. Soluble factors contained in culture medium and serum were measured by ELISA. Results We found that sorafenib inhibited the viability of macrophages accompanied by morphological changes characteristic of autophagy. This autophagy-inducing effect was validated by LC3B-I lipidation and autophagosome accumulation. The surface antigen expression and the function of activated macrophages were inhibited by sorafenib, including the expression of co-stimulatory molecule CD80, phagocytosis, and the production of reactive oxygen species. The secretion of IL-10, but not IL-6, TNF-α nor TGF-β, was reduced by sorafenib. Conclusion Sorafenib, in addition to being a cancer targeted therapeutic agent, can induce autophagy and modulate the function of human macrophages.

Original languageEnglish
Pages (from-to)333-339
Number of pages7
JournalInternational Immunopharmacology
Volume15
Issue number2
DOIs
Publication statusPublished - Feb 2013

Keywords

  • Autophagy
  • Macrophage
  • Sorafenib

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Pharmacology

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    Lin, J. C., Liu, C. L., Lee, J. J., Liu, T. P., Ko, W. C., Huang, Y. C., Wu, C. H., & Chen, Y. J. (2013). Sorafenib induces autophagy and suppresses activation of human macrophage. International Immunopharmacology, 15(2), 333-339. https://doi.org/10.1016/j.intimp.2013.01.006