Lactonic Sophorolipids Increase Tumor Burden in Apcmin+/- Mice

PLoS One. 2016 Jun 6;11(6):e0156845. doi: 10.1371/journal.pone.0156845. eCollection 2016.

Abstract

Sophorolipids (SL) are amphiphilic biosurfactant molecules consisting of a disaccharide sophorose with one fatty acid at the C1 position and optional acetylation at the C6'and C6" positions. They exist in a closed ring lactonic (LSL) or open acidic (ASL) structure Sophorolipids are produced in crude mixtures in economically viable amounts by the yeast Starmerella bombicola and used in a variety of consumer products. Varying levels of anti- proliferative and anti-cancer activity of crude sophorolipid mixtures are described in a number of tumor cell lines in vitro. However, significant inter-study variation exists in the composition of sophorolipid species as well as other biologically active compounds in these mixtures, which makes interpretation of in vitro and in vivo studies difficult. We produced a 96% pure C18:1 lactonic sophorolipid that dose-dependently reduces the viability of colorectal cancer, as well as normal human colonic and lung cell lines in vitro. Oral administration of vehicle-only; or lactonic sophorolipids (50 mg/kg for 70 days), to Apcmin+/- mice resulted in an increase in the number (55.5 ± 3.3 vs 70.50 ± 7.8: p < 0.05) and size (modal size 2mm vs 4mm) of intestinal polyps. Lactonic administration resulted in a systematic effect via reduced hematocrit (49.5 ± 1.0 vs 28.2 ± 2.0 vs: p<0.03) and splenomegaly (0.56 ± 0.03g vs 0.71 ± 0.04g; p<0.01) confirming exacerbation of disease progression in this model.

MeSH terms

  • Animals
  • Ascomycota / chemistry
  • Caco-2 Cells
  • Cell Extracts / isolation & purification
  • Cell Extracts / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology*
  • Female
  • Genes, APC
  • Glycolipids / pharmacology*
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • Male
  • Mice
  • Mice, Transgenic
  • Tumor Burden / drug effects*
  • Up-Regulation / drug effects

Substances

  • Cell Extracts
  • Glycolipids
  • 16-(2'-O-glucopyranosylglucopyranosyloxy)hexadecanoic acid 1',4''-lactone 6',6''-diacetate

Grants and funding

This research was funded by the European FP7 Project Biosurfing, Grant number 289219. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.