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We previously showed how triterpene saponin bacopaside (bac) II, purified from the medicinal herb <i>Bacopa monnieri</i>, 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 Ca²⁺ levels and plasma membrane integrity. Combined bac I and II, each applied at concentrations below IC₅₀ values, 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 Ca²⁺ was 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 Ca²⁺ flux. These in vitro findings support further research into the mechanisms of action of the combined compounds for potential clinical use.