Punicic Acid Triggers Ferroptotic Cell Death in Carcinoma Cells
(2021) Nutrients — Vol. 13, n° 8, p. 2751 [1-16] (2021)
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- Plant-derived conjugated linolenic acids (CLnA) have been widely studied for their preventive and therapeutic properties against diverse diseases such as cancer. In particular, punicic acid (PunA), a conjugated linolenic acid isomer (C18:3 c9t11c13) present at up to 83% in pomegranate seed oil, has been shown to exert anti-cancer effects, although the mechanism behind its cytotoxicity remains unclear. Ferroptosis, a cell death triggered by an overwhelming accumulation of lipid peroxides, has recently arisen as a potential mechanism underlying CLnA cytotoxicity. In the present study, we show that PunA is highly cytotoxic to HCT-116 colorectal and FaDu hypopharyngeal carcinoma cells grown either in monolayers or as three-dimensional spheroids. Moreover, our data indicate that PunA triggers ferroptosis in carcinoma cells. It induces significant lipid peroxidation and its effects are prevented by the addition of ferroptosis inhibitors. A combination with docosahexaenoic acid (DHA), a known polyunsaturated fatty acid with anticancer properties, synergistically increases PunA cytotoxicity. Our findings highlight the potential of using PunA as a ferroptosis-sensitizing phytochemical for the prevention and treatment of cancer.
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Vermonden, P., Vancoppenolle, M., Dierge, E., Mignolet, E., Cuvelier, G., Knoops, B., Page, M., Debier, C., Feron, O., & Larondelle, Y. (2021). Punicic Acid Triggers Ferroptotic Cell Death in Carcinoma Cells. Nutrients, 13(8), 2751 [1-16]. https://doi.org/10.3390/nu13082751 (Original work published 2021)