In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice

Seeram, Navindra P.; Adams, Lynn S.; Henning, Susanne M.; Niu, Yantao; Zhang, Yanjun; Nair, Muraleedharan G.; Heber, David

doi:10.1016/j.jnutbio.2005.01.006

« Previous Next »The Journal of Nutritional Biochemistry
Volume 16, Issue 6 , Pages 360-367, June 2005

In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice

Navindra P. Seeram
- Center for Human Nutrition, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
- Corresponding author. Tel.: +1 310 825 6150; fax: +1 310 206 5264.
Lynn S. Adams
- Center for Human Nutrition, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
Susanne M. Henning
- Center for Human Nutrition, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
Yantao Niu
- Center for Human Nutrition, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
Yanjun Zhang
- Bioactive Natural Products and Phytoceuticals, National Food Safety and Toxicology Center, Michigan State University, East Lansing, MI 48824, USA
- Department of Horticulture, Michigan State University, East Lansing, MI 48824, USA
Muraleedharan G. Nair
- Bioactive Natural Products and Phytoceuticals, National Food Safety and Toxicology Center, Michigan State University, East Lansing, MI 48824, USA
- Department of Horticulture, Michigan State University, East Lansing, MI 48824, USA
David Heber
- Center for Human Nutrition, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA

Received 10 December 2004

Abstract

Pomegranate (Punica granatum L.) fruits are widely consumed as juice (PJ). The potent antioxidant and anti-atherosclerotic activities of PJ are attributed to its polyphenols including punicalagin, the major fruit ellagitannin, and ellagic acid (EA). Punicalagin is the major antioxidant polyphenol ingredient in PJ. Punicalagin, EA, a standardized total pomegranate tannin (TPT) extract and PJ were evaluated for in vitro antiproliferative, apoptotic and antioxidant activities. Punicalagin, EA and TPT were evaluated for antiproliferative activity at 12.5–100 μg/ml on human oral (KB, CAL27), colon (HT-29, HCT116, SW480, SW620) and prostate (RWPE-1, 22Rv1) tumor cells. Punicalagin, EA and TPT were evaluated at 100 μg/ml concentrations for apoptotic effects and at 10 μg/ml concentrations for antioxidant properties. However, to evaluate the synergistic and/or additive contributions from other PJ phytochemicals, PJ was tested at concentrations normalized to deliver equivalent amounts of punicalagin (w/w). Apoptotic effects were evaluated against the HT-29 and HCT116 colon cancer cell lines. Antioxidant effects were evaluated using inhibition of lipid peroxidation and Trolox equivalent antioxidant capacity (TEAC) assays. Pomegranate juice showed greatest antiproliferative activity against all cell lines by inhibiting proliferation from 30% to 100%. At 100 μg/ml, PJ, EA, punicalagin and TPT induced apoptosis in HT-29 colon cells. However, in the HCT116 colon cells, EA, punicalagin and TPT but not PJ induced apoptosis. The trend in antioxidant activity was PJ>TPT>punicalagin>EA. The superior bioactivity of PJ compared to its purified polyphenols illustrated the multifactorial effects and chemical synergy of the action of multiple compounds compared to single purified active ingredients.

Keywords: Pomegranates, Punicalagin, Ellagic acid, Antiproliferative, Apoptosis, Antioxidant