In Vitro Synergistic Inhibition of HT-29 Proliferation and 2H-11 and HUVEC Tubulogenesis by Bacopaside I and II Is Associated with CaFlux and Loss of Plasma Membrane Integrity.
Pharmaceuticals (Basel). 2021 May 6 ;14(5). Epub 2021 May 6. PMID: 34066415
We previously showed how triterpene saponin bacopaside (bac) II, purified from the medicinal herb, induced cell death in colorectal cancer cell lines and reduced endothelial cell migration and tube formation, and further demonstrated a synergistic effect of a combination of bac I and bac II on the inhibition of breast cancer cell line growth. Here, we assessed the effects of bac I and II on the colorectal cancer HT-29 cell line, and mouse (2H-11) and human umbilical vein endothelial cell (HUVEC) lines, measuring outcomes including cell viability, proliferation, migration, tube formation, apoptosis, cytosolic Calevels and plasma membrane integrity. Combined bac I and II, each applied at concentrations below ICvalues, caused a synergistic reduction of the viability and proliferation of HT-29 and endothelial cells, and impaired the migration of HT-29 and tube formation of endothelial cells. A significant enhancement of apoptosis was induced only in HUVEC, although an increase in cytosolic Cawas detected in all three cell lines. Plasma membrane integrity was compromised in 2H-11 and HUVEC, as determined by an increase in propidium iodide staining, which was preceded by Caflux. These in vitro findings support further research into the mechanisms of action of the combined compounds for potential clinical use.