The Purified Extract from the Medicinal Plant Bacopa monnieri, Bacopaside II, Inhibits Growth of Colon Cancer Cells In Vitro by Inducing Cell Cycle Arrest and Apoptosis

Abstract

Aquaporin-1 (AQP1), a transmembrane pore-forming molecule, facilitates the rapid movement of water and small solutes across cell membranes. We have previously shown that bacopaside II, an extract from the medicinal herb Bacopa monnieri, blocks the AQP1 water channel and impairs migration of cells that express AQP1. The aim of this study was to further elucidate the anti-tumour potential of bacopaside II in colon cancer cells. Expression of AQP1 in HT-29, SW480, SW620 and HCT116 was determined by quantitative PCR and western immunoblot. Cells were treated with bacopaside II, and morphology, growth, autophagy, cell cycle and apoptosis assessed by time-lapse microscopy, crystal violet, acridine orange, propidium iodide (PI) and annexin V/PI staining respectively. AQP1 expression was significantly higher in HT-29 than SW480, SW620 and HCT116. Bacopaside II significantly reduced growth at ≥20 µM for HT-29 and ≥15 µM for SW480, SW620 and HCT116. Inhibition of HT-29 at 20 µM was primarily mediated by G0/G1 cell cycle arrest, and at 30 µM by G2/M arrest and apoptosis. Inhibition of SW480, SW620 and HCT116 at ≥15 µM was mediated by G2/M arrest and apoptosis. These results are the first to show that bacopaside II inhibits colon cancer cell growth by inducing cell cycle arrest and apoptosis.

Combined Systematic Review and Transcriptomic Analyses of Mammalian Aquaporin Classes 1 to 10 as Biomarkers and Prognostic Indicators in Diverse Cancers

“…AQP1 is upregulated from early through late stages of colorectal carcinogenesis, and expression levels have been suggested to correlate with tumor invasiveness, prompting classification of AQP1 as a negative prognostic indicator of patient survival [ 56 , 117 , 118 ]. Molecular knockdown and pharmacological inhibition of AQP1 in colon cancer cells significantly impaired migration, supporting AQP1 as a candidate target for colon cancer therapy [ 118 , 119 , 120 , 121 , 122 , 123 ]. Effects on motility could arise from AQP1-associated effects on actin organization via RhoA and Rac signaling pathways [ 123 ].…”

<p>Isobavachalcone isolated from <em>Psoralea corylifolia</em> inhibits cell proliferation and induces apoptosis via inhibiting the AKT/GSK-3&beta;/&beta;-catenin pathway in colorectal cancer cells</p>

“…A gap in addressing the killing of all cancer cells through chemotherapy is highlighted in the number of fatalities seen with CRC 18. When evaluating the chemotherapeutic agents used to treat CRC, a number of studies have evaluated natural products, which tend to present fewer adverse effects 19–21. One such example is an active molecule called IBC, which belongs to the group of flavonoids that is present in the well-known traditional Chinese medicinal herb Psoralea corylifolia .…”

Bumetanide-Derived Aquaporin 1 Inhibitors, AqB013 and AqB050 Inhibit Tube Formation of Endothelial Cells through Induction of Apoptosis and Impaired Migration In Vitro

“…Necrosis controls were prepared by heating harvested cells to 63 °C for 30 min. Cells were treated with endothelial growth medium, vehicle (DMSO), AqB050 at 40 and 80 µM or AqB013 plus AqB050 at 20/20 and 40/40 µM for 24 h. Harvested cells were stained with Annexin-V-FLUOS staining kit (Roche Diagnostics, Mannheim, Germany) as per the manufacturer’s instruction and fluorescence was read on BD FACSCanto II cell analyser (BD Biosciences, San Jose, CA, USA), and analysed using FlowJo software (FlowJo, Ashland, OR, USA) v10.4 as described previously [37].…”