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.

Highlights

  • Worldwide, colorectal cancer (CRC) is the third most commonly diagnosed cancer and is a leading cause of cancer-related deaths [1]

  • Expression of AQP1 was determined by quantitative PCR and western immunoblot in the untreated colon cancer cell lines HT-29, HCT116, SW480, and SW620

  • (30–40 kDa) forms (Supplementary Figure S2), the predominant form observed in colon cancer cell lines was the 56 kDa dimer, consistent with previous reports describing AQP1 in red blood cells (RBC), HT-29, SW480 and HCT116 [12,15,19]

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Summary

Introduction

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and is a leading cause of cancer-related deaths [1]. Up to 25% of patients diagnosed with early localised (stage I or II) disease and 50% with regional spread to lymph nodes or adjacent organs (stage III) eventually relapse with overt metastatic disease following surgery with curative intent [2]. Despite recent advances in treatment, patients with metastatic disease currently have 5-year survival rates of less than 15%, and a median overall survival. There is a need to improve treatment regimens for patients with, or at risk of developing, metastatic CRC. Commonly known as Brahmi, has been used in Ayurvedic medicine for thousands of years as a memory enhancer, sedative, analgesic, anti-epileptic and anti-inflammatory agent

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