Steroidal glycoalkaloids from Solanum lyratum inhibit the pro-angiogenic activity of A549-derived exosomes

Fitoterapia. 2020 Mar:141:104481. doi: 10.1016/j.fitote.2020.104481. Epub 2020 Jan 15.

Abstract

In this study, seven previously undescribed steroidal glycoalkaloids, compounds 1-7, were isolated from Solanum lyratum, along with two known ones (8 and 9). Comprehensive spectroscopy techniques were used to determine their structures. Although 1-8 only showed a weak inhibitory effect on the proliferation of the tumor-derived vascular endothelial cells, however, in a former study we found both total steroidal glycoalkaloids from Solanum lyratum (TSGS) and 9 significantly inhibited tumor angiogenesis and its mechanism was linked to its ability to interfere with cell membrane lipid rafts. Lipid rafts are closely related to the functions of tumor-derived exosomes, a vital factor in cancer progression. Thus, we investigated the impacts of TSGS and 9 on the functions of A549-derived exosomes. Our results indicated that A549-derived exosomes can significantly enhance the angiogenesis abilities of human umbilical vein endothelial cells, whereas the intervention of TSGS or 9 significantly inhibited this activity of A549-derived exosomes. These findings suggest that TSGS and 9 exert anti-tumor angiogenesis by inhibiting the pro-angiogenic activity of A549-derived exosomes.

Keywords: Angiogenesis; Exosome; Lipid raft; Solanum lyratum; Steroidal glycoalkaloid.

MeSH terms

  • A549 Cells
  • Alkaloids / chemistry*
  • Alkaloids / classification
  • Alkaloids / pharmacology*
  • Exosomes / drug effects*
  • Humans
  • Molecular Structure
  • Neovascularization, Physiologic / drug effects*

Substances

  • Alkaloids