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Novel Formulation of Undecylenic Acid induces Tumor Cell Apoptosis

journal contribution
posted on 23.11.2022, 22:45 authored by Zoe DayZoe Day, Alyce MayfoshAlyce Mayfosh, Marie-Claire Giel, Yuning HongYuning Hong, Scott WilliamsScott Williams, Jascinta P Santavanond, Thomas F Rau, Ivan K Poon, Mark HulettMark Hulett
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.

Funding

This work was supported by a Cooperative Research Centre project (CRC-P) grant from AusIndustry, Department of Industry, Science, Energy and Resources. Funding number CRCPSEVEN000177

History

Publication Date

16/11/2022

Journal

International Journal of Molecular Sciences

Volume

23

Issue

22

Pagination

22p.

Publisher

MDPI AG

Rights Statement

© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)

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