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Anti-Proliferative and Anti-Telomerase Effects of Blackberry Juice and Berry- Derived Polyphenols on HepG2 Liver Cancer Cells and Normal Human Blood Mononuclear Cells

[ Vol. 22 , Issue. 2 ]

Author(s):

Delaram Moghadam, Reza Zarei, Mohsen Tatar, Zahra Khoshdel, Farideh Jalali Mashayekhi and Fakhraddin Naghibalhossaini*   Pages 395 - 403 ( 9 )

Abstract:


Background: Previous studies have provided strong evidence for the anticancer activity of berry fruits. <p> Objective: In this study, we investigated the effects of blackberry juice and three berry- polyphenolic compounds on cell proliferation and telomerase activity in human hepatoma HepG2 and normal peripheral blood mononuclear cells (PBMCs). <p> Methods: The cell viability and telomerase activity were measured by MTT and TRAP assay, respectively. Berry effects on the expression of genes were determined by quantitative RT-PCR assay. <p> Results: Blackberry, gallic acid, and resveratrol inhibited proliferation of both HepG2 and PBMC cells in a dosedependent manner. Resveratrol was more effective than gallic acid for reducing the viability of HepG2 cells, but both showed the same level of growth inhibition in PBMC cells. Berry, resveratrol, and gallic acid significantly inhibited telomerase activity in HepG2 cells. The antiproliferative effect of berry was associated with apoptotic DNA fragmentation. Gallic acid was more effective for reducing telomerase activity than resveratrol, but anthocyanin moderately increased telomerase activity in cancer cells. Telomerase activity was induced by all three polyphenols in PBMCs. Overall, Krumanin chloride was more effective to induce telomerase than gallic acid and resveratrol in PBMC cells. There was no significant difference in <i>hTERT, hTR</i>, and Dnmts expressions between berry treated and the control untreated HepG2 cells. But, a significant downregulation of <i>HDAC1</i> and <i>HDAC2</i> and upregulation of <i>SIRT1</i> were observed in berry-treated cells. <p> Conclusion: These data indicate that the berry anticancer effect is associated with antitelomerase activity and changes in HDACs expression. The data also suggest that berry antitelomerase activity is mainly related to its gallic acid and resveratrol, but not anthocyanin content.

Keywords:

Blackberry, polyphenols, anthocyanin, resveratrol, gallic acid, anticancer, telomerase.

Affiliation:

Department of Biochemistry, Shiraz University of Medical Sciences, School of Medicine, Shiraz, Department of Biochemistry, Shiraz University of Medical Sciences, School of Medicine, Shiraz, Department of Biochemistry, Shiraz University of Medical Sciences, School of Medicine, Shiraz, Department of Biochemistry, Shiraz University of Medical Sciences, School of Medicine, Shiraz, Department of Biochemistry and Genetics, School of Medicine, Arak University of Medical Sciences, Arak, Department of Biochemistry, Shiraz University of Medical Sciences, School of Medicine, Shiraz

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