University of Minnesota, Hormel Institute, Austin, MN 55912-3679, USA.
Int J Oncol. 2010 Feb;36(2):421-6.
Pomegranate extracts have been used as anticancer agents and they contain a large number of potentially bioactive substances. Punicic acid is an omega-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 (MDA-MB-231) and an estrogen sensitive cell line developed from the MDA-MB-231 cells (MDA-ERalpha7). Proliferation was inhibited 92 and 96% for MDA-MB-231 and MDA-ERalpha7 cells, respectively compared to untreated cells by 40 microM punicic acid. Furthermore, punicic acid induced apoptosis in the MDA-MB-231 and MDA-ERalpha7 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 microM 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-ERalpha7 cells. These results suggest that punicic acid has breast cancer inhibitor properties that are dependent on lipid peroxidation and the PKC pathway.
石榴提取物已被用作抗癌剂，其中含有大量具有潜在生物活性的物质。 punnic 酸是一种在石榴籽油中发现的 omega-5 长链多不饱和脂肪酸。据报道，许多长链脂肪酸具有预防癌症的作用。在这里，我们研究了 punnic 酸影响两种雌激素不敏感乳腺癌细胞系（MDA-MB-231）和从 MDA-MB-231 细胞系（MDA-ERalpha7）发育而来的雌激素敏感细胞系生长的潜力。与未经处理的细胞相比，40 μM punnic 酸分别使 MDA-MB-231 和 MDA-ERalpha7 细胞的增殖抑制了 92%和 96%。此外，与未经处理的对照细胞相比，punic 酸分别使 MDA-MB-231 和 MDA-ERalpha7 细胞的凋亡增加了 86%和 91%，并破坏了细胞线粒体膜电位。我们还通过向测定中添加 20 μM 抗氧化剂 tocotrienol 来研究脂质氧化是否是 punnic 酸功能所必需的。这导致 punnic 酸对增殖抑制、凋亡和线粒体膜电位破坏的作用逆转。最后，我们通过在存在蛋白激酶 C（PKC）抑制剂双吲哚马来酰亚胺 I 的情况下进行增殖测定，评估了 PKC 信号在 punnic 酸抗癌作用中的作用。 punnic 酸对 MDA-MB-231 和 MDA-ERalpha7 细胞的增殖抑制作用部分被阻断。这些结果表明，punic 酸具有依赖于脂质过氧化和 PKC 途径的乳腺癌抑制剂特性。
