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In vitro synergistic inhibition of HT-29 proliferation and 2H-11 and HUVEC tubulogenesis by bacopaside I and II is associated with Ca²⁺ flux and loss of plasma membrane integrity

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journal contribution
posted on 2024-06-19, 06:44 authored by Y Tomita, E Smith, HM Palethorpe, M Nakhjavani, KKL Yeo, AR Townsend, TJ Price, AJ Yool, JE Hardingham
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.

History

Journal

Pharmaceuticals

Volume

14

Article number

436

Pagination

1-18

Location

Basel, Switzerland

Open access

  • Yes

ISSN

1424-8247

eISSN

1424-8247

Language

eng

Publication classification

C1 Refereed article in a scholarly journal

Issue

5

Publisher

MDPI AG