Punicic acid is an ω-5 fatty acid capable of inhibiting breast cancer proliferation

Abstract

Abstract. Pomegranate extracts have been used as anticancer agents and they contain a large number of potentially bioactive substances. Punicic acid is an ˆ-5 long chain polyunsaturated fatty acid found in Punica granatum (pomegranate) seed oil. A number of long chain fatty acids have been reported to have cancer preventive actions. Here we investigated the potential ability of punicic acid to affect growth of both an estrogen insensitive breast cancer cell line and an estrogen sensitive cell line developed from the MDA-MB-231 cells (MDA-ER·7). Proliferation was inhibited 92 and 96% for MDA-MB-231 and MDA-ER·7 cells, respectively compared to untreated cells by 40 μM punicic acid. Furthermore, punicic acid induced apoptosis in the MDA-MB-231 and MDA-ER·7 cells by 86 and 91%, respectively compared to untreated control cells and disrupted cellular mitochondrial membrane potential. We also investigated whether lipid oxidation was required for the function of punicic acid by adding 20 μM of the antioxidant tocotrienol to the assays. This resulted in reversal of the effects of punicic acid on proliferation inhibition, apoptosis and disruption of the mitochondrial membrane potential. Finally, we evaluated the role of PKC signaling in the anti-cancer effects of punicic acid by performing proliferation assays in the presence of the PKC inhibitor bisindolymaleimide I. Proliferation inhibition by punicic acid was partially blocked in both the MDA-MB-231 and MDA-ER·7 cells. These results suggest that punicic acid has breast cancer inhibitor properties that are dependent on lipid peroxidation and the PKC pathway. IntroductionPomegranate (punica granatum) is a well known alternative medicine and various extracts from pomegranate are utilized as supplements with a wide variety of purported health benefits including anticancer actions (1). These supplements contain a number of different components that under some conditions either activate or inhibit estrogen, lower oxidation of LDL cholesterol, reduce arterial plaques, lower oxidative stress, enhance wound healing, inhibit angiogenesis, inhibit tumor proliferation and increase tumor apoptosis (1-3). However, these studies have been conducted with fruit, seeds, pericarp or partially purified extracts making it hard to determine what the active component(s) of pomegranate may be.Dietary fats may be capable of anticancer effects, particularly in the case of breast cancer. There are a number of different types of fatty acids including long chain polyunsaturated fatty acids (LC-PUFA) known to be capable of cancer inhibition. Conjugated linoleic acid (CLA) and the omega 3 (ˆ-3) LC-PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) that are found in fish oil have been the most widely studied (4-6). However, a less examined group of rare omega 5 (ˆ-5) LC-PUFAs may have even greater cancer inhibition properties. Punicic acid (PA), also known as 9Z,11E,13Z-octadecatrienoic acid, is an ˆ-5 LC-PUFA that makes up approximately 65-80% of the oil from pomegranate seeds (7), i...

Conjugated linolenic acid (CLnA) isomers as new bioactive lipid compounds in ruminant-derived food products. A review

“…Cytotoxic effect of CLnA isomers of conjugated triene type was more evident than this of conjugated diene type, which is partially conjugated (Koba et al, 2007a). It is said that the mechanism of cytotoxic effect of CLnA is connected with the lipid peroxidation, which causes an activation of protein kinase C (PKC) responsible for apoptosis induction and proliferation inhibition (Grossmann et al, 2010). Nevertheless, the addition of antioxidant compounds (e.g., α-tocopherol) decreased these beneficial properties of CLnA isomers (Shinohara et al, 2012).…”

Punicic Acid Triggers Ferroptotic Cell Death in Carcinoma Cells

“…In fact, CLnAs have been shown to possess anti-inflammatory [14][15][16], anti-obesity [14,17,18], anti-diabetic [19,20] and anti-cancer activities [1,2,[21][22][23]. Specifically, PunA has been reported to exert a strong anti-cancer activity, both in vitro [7,[24][25][26] and in vivo [4,27,28]. PunA anti-cancer activity is thought to be associated with lipid peroxidation [7].…”

Thermal processing of pomegranate seed oils underscores their antioxidant stability and nutritional value: Comparison of pomegranate seed oil with sesame seed oil

“…These acids are rarely found in animal fats and are not commonly found in vegetable oils (Özgül‐Yücel, 2005 ). Studies have shown punicic acid has beneficial health effects such as antitumor activities, immune system regulators, anti‐atherosclerosis, and serum lipid lowering (Carvalho et al., 2010 ; Grossmann et al., 2010 ). Therefore, with high levels of punicic acid, the studied pomegranate seed oil may also have health‐benefiting properties.…”

“…Several studies have reported on the levels of phenolics in pomegranate seed oils. Phenolics of seed oils of six pomegranate cultivars grown in Georgia ranged from 849 to 911 mg/kg (Grossmann et al., 2010 ). In other studies, phenolics of pomegranate seed oils grown in South Africa (Kaseke et al., 2021 ) and Serbia (Drinić et al., 2020 ) were reported at 1200 and 160 mg/kg, respectively.…”