Punicic acid is an omega-5 fatty acid capable of inhibiting breast cancer proliferation.
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.
Grossmann
Michael E
ME
University of Minnesota, Hormel Institute, Austin, MN 55912-3679, USA.
Mizuno
Nancy K
NK
Schuster
Todd
T
Cleary
Margot P
MP
D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D005227:Fatty Acids / Q000494:pharmacology; D005260:Female; D006801:Humans; D008042:Linolenic Acids / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D029561:Lythraceae / Q000737:chemistry; D010936:Plant Extracts / Q000494:pharmacology*; D011493:Protein Kinase C
D000970:Antineoplastic Agents; D000975:Antioxidants; D005227:Fatty Acids; D008042:Linolenic Acids; D010936:Plant Extracts; D011493:Protein Kinase C; C519714:punicic acid