Selenium-lentinan inhibits tumor progression by regulating epithelial-mesenchymal transition

Toxicol Appl Pharmacol. 2018 Dec 1:360:1-8. doi: 10.1016/j.taap.2018.09.019. Epub 2018 Sep 18.

Abstract

Background: Selenium supplementation can be used to treat tumors. However, inorganic selenium is highly toxic, and natural organic selenium is extremely rare. Polysaccharides can improve drug bioavailability and targeting. Lentinan is a polysaccharide that has been approved as an anti-cancer drug in Japan and China.

Methods: Lentinan, an antitumor polysaccharide extracted from Lentinus edodes, was conjugated with seleninic acid to be transformed into ester (Se-lentinan) and utilized as drug carrier. The enhancement of the anti-tumor effects of Se-lentinan was evaluated by cell viability, cell cycle, migration, and transwell assays and animal xenograft models. The effects of Se-lentinan on the expression levels of epithelial-mesenchymal transition (EMT) markers were determined through immunofluorescence, Western blot, and immunohistochemistry analyses.

Results: Se-lentinan inhibited the invasiveness of B16-BL6 and HCT-8 cells by suppressing EMT. In vivo, Se-lentinan significantly inhibited tumor growth and metastasis of the transplanted melanoma and colon cancer cells and showed less toxicity than sodium selenite. Moreover, Se-lentinan reduced the accumulation of selenium in the liver and kidney tissues of mice and exhibited low organ toxicity.

Conclusion: The antitumor activity of selenium was enhanced greatly, and its side effects were reduced with the use of lentinan as drug carrier.

Keywords: Epithelial–mesenchymal transition; Lentinan; Selenium; Tumor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cell Cycle / drug effects
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Disease Progression
  • Epithelial-Mesenchymal Transition / drug effects*
  • HEK293 Cells
  • Humans
  • Lentinan / pharmacology*
  • MCF-7 Cells
  • Melanoma, Experimental / drug therapy
  • Mice
  • NIH 3T3 Cells
  • Neoplasm Metastasis / drug therapy
  • Polysaccharides / pharmacology
  • Selenium / pharmacology*
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Polysaccharides
  • Lentinan
  • Selenium