Pomegranate (Punica granatum) Seed Linolenic Acid Isomers: Concentration-Dependent Modulation of Estrogen Receptor Activity

Abstract

Pomegranate (Punica granatum) seed linolenic acid isomers were evaluated as selective estrogen receptor modulators (SERMs) in vitro. Punicic acid (PA) inhibited (IC₅₀) estrogen receptor (ER) α at 7.2 μM, ERβ at 8.8 μM; α-eleostearic acid (AEA) inhibited ERα/ERβ at 6.5/7.8 μM. PA (not AEA) agonized ERα/ERβ (EC₅₀) at 1.8/2 μM, antagonizing at 101/80 μM. AEA antagonized ERα/ERβ at 150/140 μM. PA and AEA induced ERα and ERβ mRNA expression in MCF-7, but not in MDA-MB-231. Overall, the results show PA and AEA are SERMs.

Keywords:

• Breast cancer
• Conjugated linolenic acid
• Phytoestrogen
• Pomegranate (Punica granatum)
• Proliferation
• Punicic acid
• Selective estrogen receptor modulator

ACKNOWLEDGMENTS

This work was supported by the Grant of Agricultural R&D Promotion center (ARPC, 2002–2005), Republic of Korea. We thank Professor Gunter Daxenbichler, Univ-Klink fur Frauenheikunde, Innsbruck, Germany for the kind gift of breast cancer cell lines.

DECLARATION OF INTEREST

The authors report no conflicts of interest. Drs. Lansky and Newman are co-developing a complex anticancer pharmaceutical from pomegranate fruit under the auspices of Punisyn Pharmaceuticals, Ltd. The authors alone are responsible for the content and writing of the paper.