Polyphenols are responsible for the proapoptotic properties of pomegranate juice on leukemia cell lines
Article first published online: 20 FEB 2013
© 2013 The Authors. Food Science & Nutrition published by Wiley Periodicals, Inc.
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Food Science & Nutrition
Volume 1, Issue 2, pages 196–208, March 2013
How to Cite
Food Science & Nutrition 2013; 1(2): 196–208
- Issue published online: 14 MAR 2013
- Article first published online: 20 FEB 2013
- Manuscript Accepted: 6 JAN 2013
- Manuscript Revised: 17 DEC 2012
- Manuscript Received: 19 SEP 2012
- Saudi Ministry of Health
Pomegranates have shown great promise as anti-cancer agents in a number of cancers including clinical trials in prostate cancer. We have previously shown pomegranate juice (PGJ) induced apoptosis and preferentially alters the cell cycle in leukemia cell lines compared with nontumor control cells. However, the agents responsible have not yet been fully elucidated. Treatment of four leukemia cell lines with five fractions obtained from PGJ by solid phase extraction demonstrated that only the acetonitrile fractions decreased adenosine triphosphate (ATP) levels in all leukemia cell lines. Acetonitrile fractions also significantly activated caspase-3 and induced nuclear morphology characteristic of apoptosis. S phase arrest was induced by acetonitrile fractions which matched S phase arrest seen previously following whole PGJ treatments. The acetonitrile fractions contained higher phenol content than whole PGJ whereas only low levels of phenols were seen in any other fraction. Liquid chromatography mass spectrometry (LC–MS) analysis demonstrated that acetonitrile fractions were enriched in ellagitannins, ellagic acid, and hydroxycinnamic acid derivatives but depleted in anthocyanins. Individual treatments with identified compounds demonstrated that the ellagitannin: punicalagin was the most active and mimicked the responses seen following acetonitrile fraction treatment. Bioactive components within pomegranate were confined to the acetonitrile fraction of PGJ. The enrichment in ellagitannins and hydroxycinnamic acids suggest these may provide the majority of the bioactivities of PGJ. Individual treatments with compounds identified demonstrated that the ellagitannin: punicalagin was the most active agent, highlighting this compound as a key bioactive agent in PGJ.