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

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.