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

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Lakshmanan, Jaganathan, Jaganathan, Vaitheesh L., Zhang, Boachun, Werner, Grace, Allen, Tyler S., Schultz, David J., Klinge, Carolyn M., Harbrecht, Brian G.·2025·Anti-Cancer Agents in Medicinal Chemistry
DOI 10.2174/0118715206327789241008162423PMC PMC11965954
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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.

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Metadata

Authors
Lakshmanan, J., Jaganathan, V. L., Zhang, B., Werner, G., Allen, T. S., Schultz, D. J., Klinge, C. M., & Harbrecht, B. G.
Affiliations
University of Louisville (US)
Corresponding author
Lakshmanan, Jaganathan
ORCID
Venue
Anti-Cancer Agents in Medicinal Chemistry
Publisher
Bentham Science Publishers Ltd.
Published
2025-02
Volume
25
Issue
3
Pages
207-221
ISSN
  • 1568-0118 (ISSN-L)
  • 1871-5206
DOI
10.2174/0118715206327789241008162423
PMC
PMC11965954
OpenAlex
W4403478915
Cited by
5
References
6
Citations by year
2026: 3 · 2025: 2
FWCI
0.55
Type
journal article
Language
en
Open access
Locations
  • Anti-Cancer Agents in Medicinal Chemistry (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
Funders
NIH NIDDK T35 Training Grant (T35 DK072923)
Topics
  • Life Sciences › Agricultural and Biological Sciences › Food Science › Coconut Research and Applications
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Medicinal Plant Research
  • Physical Sciences › Chemistry › Organic Chemistry › Phytochemical Studies and Bioactivities
Keywords
tender coconut water, anticancer activity, hepatocellular carcinoma, epithelial-mesenchymal transition, Akt signaling, ERK signaling, ZEB1, E-cadherin, N-cadherin, breast cancer, colon cancer, untargeted metabolomics, caffeic acid, polyketides, phenylpropanoids, lipid metabolites
MeSH terms
Antineoplastic Agents, Antineoplastic Agents, Phytogenic, Cell Survival, Cocos, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Humans, Plant Extracts, Structure-Activity Relationship, Tumor Cells, Cultured, Molecular Structure, Cell Line, Tumor, Cell Proliferation, Metabolomics

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