Abstract A72: Punicic acid, a fatty acid from pomegranate seed oil, inhibits breast cancer cell proliferation

Abstract

Abstract Introduction: Pomegranate (Punica granatum) is a well-known fruit used for alternative medicine. Various pomegranate extracts are utilized as supplements with a wide variety of purported health benefits including anticancer actions. These supplements contain a number of different components that may either activate or inhibit estrogen's action. Additionally factors associated with pomegranate fruit or extracts may lower oxidation of LDL cholesterol, reduced arterial plaques, lower oxidative stress, enhanced wound healing, inhibition of angiogenesis and tumor proliferation and increased tumor apoptosis. However, these studies have been conducted with fruit, seeds, pericarp or partially purified pomegranate extracts making it hard to determine what the active component(s) may be. Punicic acid is an omega-5 long chain polyunsaturated fatty acid found in 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 (MDA-MB-231) and an estrogen sensitive cell line developed from the MDAMB-231 cells (MDA-ER 7). Methods: The two breast cancer cell lines were cultured in vitro in the presence of various amounts of punicic acid, conjugated linoleic acid, α-linolenic acid and other substances to evaluate cell proliferation, apoptosis, mitochondrial membrane permeability and cell cycle. Results: We found that 40 µM punicic acid inhibited proliferation of MDA-MB-231 and MDA-ER 7 cells 92% and 96% respectively compared to untreated cells. 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. Punicic acid also disrupted mitochondrial membrane potential of both cell lines. We next 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 in both the MDA-MB-231 and MDA-ER 7 cells. Finally, we evaluated the role of PKC signaling in the anticancer 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. Conclusions: Our in vitro assays indicated that punicic acid inhibited both estrogen sensitive and estrogen insensitive cell lines equally. Additionally the results indicate that the antiproliferative effect of punicic acid on human breast cancer cells appears to be at least partially dependent on lipid peroxidation and the PKC pathway. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A72.