Novel Formulation of Undecylenic Acid induces Tumor Cell Apoptosis

Zoe I. Day, Alyce J. Mayfosh, Marie Claire Giel, Yuning Hong, Scott A. Williams, Jascinta P. Santavanond, Thomas F. Rau, Ivan K. Poon, Mark D. Hulett

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3 Citations (Scopus)

Abstract

Undecylenic acid, a monounsaturated fatty acid, is currently in clinical use as a topical antifungal agent, however the potential for therapeutic application in other disease settings has not been investigated. In this study, we describe a novel platform for the solubilization of fatty acids using amino acids and utilize this approach to define a tumoricidal activity and underlying mechanism for undecylenic acid. We examined a novel formulation of undecylenic acid compounded with L-Arginine, called GS-1, that induced concentration-dependent tumor cell death, with undecylenic acid being the cytotoxic component. Further investigation revealed that GS-1-mediated cell death was caspase-dependent with a reduction in mitochondrial membrane potential, suggesting a pro-apoptotic mechanism of action. Additionally, GS-1 was found to localize intracellularly to lipid droplets. In contrast to previous studies where lipid droplets have been shown to be protective against fatty acid-induced cell death, we showed that lipid droplets could not protect against GS-1-induced cytotoxicity. We also found a role for Fatty Acid Transport Protein 2 (FATP2) in the uptake of this compound. Collectively, this study demonstrates that GS-1 has effective pro-apoptotic antitumor activity in vitro and, together with the novel platform of fatty acid solubilization, contributes to the re-emerging field of fatty acids as potential anti-cancer therapeutics.

Original languageEnglish
Article number14170
Number of pages22
JournalInternational Journal of Molecular Sciences
Volume23
Issue number22
DOIs
Publication statusPublished - Nov 2022
Externally publishedYes

Keywords

  • anticancer
  • apoptosis
  • cancer
  • fatty acid
  • lipid droplets
  • monounsaturated fatty acid
  • undecylenic acid

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