Peroxidation of n-3 and n-6 polyunsaturated fatty acids in the acidic tumor environment leads to ferroptosis-mediated anticancer effects

Dierge, Emeline; Debock, Elena; Guilbaud, Céline; Corbet, Cyril; Mignolet, Éric; Mignard, Louise; Bastien, Estelle; Dessy, Chantal; Larondelle, Yvan; Féron, Olivier

doi:10.1016/j.cmet.2021.05.016

Cited by 253 publications

(225 citation statements)

References 47 publications

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“…These findings suggest that PunA and DHA act in a supraadditive way to impact on carcinoma cell viability and that their combination may thus possess an interesting anti-cancer potential to be exploited in preventive or therapeutic strategies. The cytotoxicity of DHA on carcinoma cells has been shown in the past [54][55][56][57] and has been recently demonstrated on carcinoma cells under acidosis [50]. Here we show that at micromolar doses, PunA but not DHA decreases the viability of carcinoma cells grown in physiological conditions (Figure 1e,f).…”

Section: The Effect Of Puna On Carcinoma Cells Is Enhanced In the Presence Of Dhasupporting

confidence: 78%

“…A very recent study conducted by Beatty et al showed that upon incorporation into triglycerides, α-ESA triggers ferroptosis in triple negative breast cancer cells [49]. This study however is at odds with previous work from our team, where we reported that triglyceride storage has a protective effect against PUFA-induced ferroptosis [50]. More work is thus warranted to further dissect the potential pro-ferroptotic effects of PunA.…”

Section: Introductioncontrasting

confidence: 67%

“…Regarding the carcinoma cells grown as 3D spheroids, PunA cytotoxicity arose from a lower dose as compared to DHA, with a 7-fold lower dose of PunA leading to a similar (HCT-116) or stronger (FaDu) decrease in spheroid diameter as compared to DHA (Figure 1g,h). Of note, DHA 100 µM alone led to a reduction in spheroid diameter as compared to the control, likely due to its cytotoxicity on carcinoma cells facing acidosis inside the spheroids [50]. Again, HCT-116 carcinoma cells appear more sensitive to PunA than FaDu cells both in time and in cytotoxic response, with a lower final diameter for HCT-116 spheroids.…”

Section: The Effect Of Puna On Carcinoma Cells Is Enhanced In the Presence Of Dhamentioning

confidence: 90%

“…After 24 h, cell culture medium was supplemented with fixed concentrations of BSA-conjugated punicic acid (Larodan, Solna, Sweden, 10-1875) or docosahexaenoic acid (Larodan, Solna, Sweden, 10-2206), as well as of (+)-α-tocopherol (Sigma, Saint-Louis, MO, USA), ferrostatin-1 (Sigma, Saint-Louis, MO, USA), deferoxamine mesylate (Sigma, Saint-Louis, MO, USA), ZVAD-fmk (Sigma, Saint-Louis, MO, USA) or necrostatin-1 (Sigma, Saint-Louis, MO, USA) for 72 h. All compounds were dissolved in DMSO, except (+)α-tocopherol, which was dissolved in ethanol. The doses of punicic acid were chosen to cover a large range of concentrations while the doses of the other compounds were selected based on previous studies [39,41,50]. After 72 h, cell viability was determined by using Presto Blue reagent (Thermo Fisher Scientific, Waltham, MA, USA) according to manufacturer's instructions.…”

Section: Cell Viability Assessmentmentioning

confidence: 99%

“…Our data indicate that PunA induces ferroptosis in carcinoma cells by triggering an intense lipid peroxidation, a phenomenon that is prevented by ferroptosis inhibitors. In addition, a combination of PunA with docosahexaenoic acid (DHA, C22:6 c4c7c10c13c16c19), another PUFA recently shown to induce ferroptosis under acidosis [50], increases its effect in a synergistic manner. These findings suggest that PunA, possibly in combination with DHA, could be used as an anti-cancer agent.…”

Section: Introductionmentioning

confidence: 99%

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Punicic Acid Triggers Ferroptotic Cell Death in Carcinoma Cells

et al. 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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Section: The Effect Of Puna On Carcinoma Cells Is Enhanced In the Presence Of Dhasupporting

confidence: 78%

Section: Introductioncontrasting

confidence: 67%

Section: The Effect Of Puna On Carcinoma Cells Is Enhanced In the Presence Of Dhamentioning

confidence: 90%

Section: Cell Viability Assessmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Punicic Acid Triggers Ferroptotic Cell Death in Carcinoma Cells

et al. 2021

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Crosstalk between ferroptosis and stress—Implications in cancer therapeutic responses

Zhang

Yang

et al. 2022

Cancer Innovation

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Ferroptosis is a newly discovered form of cell death that is characterized by the accumulation of iron-dependent lipid peroxidation. Research on ferroptosis has seen exponential growth over the past few years. Tumor cells are strongly dependent on iron for their growth, which makes them develop mechanisms to increase iron uptake and inhibit iron output, thereby completing iron accumulation. Ferroptosis can be induced or inhibited by various stresses through multiple mechanisms, making it stands at the crossroads of stresses related cancer cell fate determination. In this review, we give a brief summary of ferroptosis hallmarks and provide a systematic analysis of the current molecular mechanisms and regulatory networks of diverse stress conditions on ferroptosis. We also discuss the relationships between ferroptosis and cancer therapy responses to further understand potential targets and therapeutic strategies for cancer treatment.

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Efficacy mechanisms research progress of the active components in the characteristic woody edible oils

Xu,

Wang,

Bai

et al. 2023

Food Frontiers

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Woody edible oils are a type of vegetable oil. Woody edible oils like olive oil have greater quantities of unsaturated fatty acids (UFAs), particularly essential FAs, as well as vitamin E, phytosterols, and other nutrients that are becoming more vital in human health. As a result, finding high‐quality woody oil resource plants is critical to ensuring enough edible oil supply. As six novel woody crops, Paeonia suffruticosa, Plukenetia volubilis, Acer truncatum, Olea europaea, Camellia sinensis, and Camellia oleifera are characterized by high oil production, widespread cultivation, adaptability, and various active ingredients. The six woody crop oils contain UFAs (e.g., α‐linolenic acid, oleic acid, and linoleic acid), vitamin E, polyphenols, phytosterols, and so forth. The presence of these active ingredients confers anti‐inflammatory, antioxidant, cholesterol and lipid metabolism regulating, blood lipid lowering, immune boosting, memory improving, intestinal flora regulating, and other properties to the oils, which are beneficial to body health. This article examined in depth the seed resources, FA composition, active component kinds, active ingredient efficacy mechanism, and physiological impacts of these six novel woody crop oils. These developments lay a solid platform for further study and development of these woody oil crops.

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Peroxidation of n-3 and n-6 polyunsaturated fatty acids in the acidic tumor environment leads to ferroptosis-mediated anticancer effects

Cited by 253 publications

References 47 publications

Punicic Acid Triggers Ferroptotic Cell Death in Carcinoma Cells

Punicic Acid Triggers Ferroptotic Cell Death in Carcinoma Cells

Crosstalk between ferroptosis and stress—Implications in cancer therapeutic responses

Efficacy mechanisms research progress of the active components in the characteristic woody edible oils

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