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Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Research Article

Anticancer Properties Against Select Cancer Cell Lines and Metabolomics Analysis of Tender Coconut Water

Author(s): Jaganathan Lakshmanan*, Vaitheesh L. Jaganathan, Boachun Zhang, Grace Werner, Tyler S. Allen, David J. Schultz, Carolyn M. Klinge and Brian G. Harbrecht

Volume 25, Issue 3, 2025

Published on: 15 October, 2024

Page: [207 - 221] Pages: 15

DOI: 10.2174/0118715206327789241008162423

Price: $65

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Abstract

Background: Tender Coconut Water (TCW) is a nutrient-rich dietary supplement that contains bioactive secondary metabolites and phytohormones with anti-oxidative and anti-inflammatory properties. Studies on TCW’s anti-cancer properties are limited and the mechanism of its anti-cancer effects have not been defined.

Objective: In the present study, we investigate TCW for its anti-cancer properties and, using untargeted metabolomics, we identify components form TCW with potential anti-cancer activity.

Methodology: Cell viability assay, BrdU incorporation assay, soft-agar assay, flow-cytometery, and Western blotting were used to analyze TCW’s anticancer properties and to identify mechanism of action. Liquid chromatography- Tandem Mass Spectroscopy (LC-MS/MS) was used to identify TCW components.

Results: TCW decreased the viability and anchorage-independent growth of HepG2 hepatocellular carcinoma (HCC) cells and caused S-phase cell cycle arrest. TCW inhibited AKT and ERK phosphorylation leading to reduced ZEB1 protein, increased E-cadherin, and reduced N-cadherin protein expression in HepG2 cells, thus reversing the ‘epithelial-to-mesenchymal’ (EMT) transition. TCW also decreased the viability of Hep3B hepatoma, HCT-15 colon, MCF-7 and T47D luminal A breast cancer (BC) and MDA-MB-231 and MDA-MB-468 triplenegative BC cells. Importantly, TCW did not inhibit the viability of MCF-10A normal breast epithelial cells. Untargeted metabolomics analysis of TCW identified 271 metabolites, primarily lipids and lipid-like molecules, phenylpropanoids and polyketides, and organic oxygen compounds. We demonstrate that three components from TCW: 3-hydroxy-1-(4-hydroxyphenyl)propan-1-one, iondole-3-carbox aldehyde and caffeic acid inhibit the growth of cancer cells.

Conclusion: TCW and its components exhibit anti-cancer effects. TCW inhibits the viability of HepG2 hepatocellular carcinoma cells by reversing the EMT process through inhibition of AKT and ERK signalling.

Keywords: Tender coconut water, HepG2, cancer, EMT, metabolomics, anti-cancer effects.

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