We investigated whether dissimilar biochemical fractions originating in anatomically discrete sections of the pomegranate (Punica granatum) fruit might act synergistically against proliferation, metastatic potential, and phosholipase A2 (PLA2) expression of human prostate cancer cells in vitro. Proliferation of DU 145 human prostate cancer cells was measured following treatment with a range of therapeutically active doses of fermented pomegranate juice polyphenols (W) and sub-therapeutic doses of either pomegranate pericarp (peel) polyphenols (P) or pomegranate seed oil (Oil). Invasion across Matrigel by PC-3 human prostate cancer cells was measured following treatment with combinations of W, P and Oil such that the total gross weight of pomegranate extract was held constant. Expression of PLA2, associated with invasive potential, was measured in the PC-3 cells after treatment with the same dosage combinations as per invasion. Supra-additive, complementary and synergistic effects were proven in all models by the Kruskal-Wallis non-parametric H test at p < 0.001 for the proliferation tests, p < 0.01 for invasion, and p < 0.05 for PLA2 expression. Proliferation effects were additionally evaluated with CompuSyn software median effect analysis and showed a concentration index CI < 1, confirming synergy. The results suggest vertical as well as the usual horizontal strategies for discovering pharmacological actives in plants.
|Number of pages||10|
|Journal||Investigational New Drugs|
|State||Published - Jan 2005|
Bibliographical noteFunding Information:
The authors wish to express their gratitude to Alexander Botvinnik for technical assistance in the preparation of the manuscript. We are also indebted to Eli Merom of Kibbutz Sde Eliahu for supplying the organically grown pomegranates, and to the late Jeffrey Marks for fermentation of the pomegranate juice. Partial assistance for this work came from the Israel Office of the Chief Scientist and the Prostate Cancer Research Fund, UK.
- complex drug
- drug design
- drug discovery
- natural product
ASJC Scopus subject areas
- Pharmacology (medical)