Abstract

We previously showed how triterpene saponin bacopaside (bac) II, purified from the medicinal herb Bacopa monnieri, 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.

Highlights

  • Herbal medicine has been used for thousands of years in many societies and takes advantage of the inherent healing properties of plants

  • A crystal violet growth assay was performed on HT-29, 2H-11 and human umbilical vein endothelial cell (HUVEC) following treatment with bac I and II, either alone or in combination

  • Bac II exhibited more cytotoxicity on 2H-11 than HT-29, and the IC50 was 105.7 μM for bac I (Figure 1B) and

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Summary

Introduction

Herbal medicine has been used for thousands of years in many societies and takes advantage of the inherent healing properties of plants. It is still a mainstay of primary health care in many parts of the world, and is used to complement more conventional medicine [1]. Bacopaside (bac) I and bac II are methanol extracts of Bacopa monnieri (BM), a herbal plant used in Ayurvedic medicine as a cognitive enhancer, sedative and anti-epileptic [4]. They belong to plant terpenoids, triterpenoid saponins, which have attracted interest as novel natural anticancer compounds with favorable efficacy and safety profiles. Several triterpenoid saponins, including Jujuboside B, senegin III and SB365, have been shown to exhibit anticancer activity using in vivo models [5,6,7]

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