Department of Biochemistry, Shiraz University of Medical Sciences, School of Medicine, Shiraz, Iran.
Department of Biochemistry and Genetics, School of Medicine, Arak University of Medical Sciences, Arak, I.R. Iran.
Anticancer Agents Med Chem. 2022;22(2):395-403. doi: 10.2174/1871520621666210315092503.
Previous studies have provided strong evidence for the anticancer activity of berry fruits.
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).
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.
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 hTERT, hTR, and Dnmts expressions between berry treated and the control untreated HepG2 cells. But, a significant downregulation of HDAC1 and HDAC2 and upregulation of SIRT1 were observed in berry-treated cells.
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.
先前的研究为浆果类水果的抗癌活性提供了有力证据。
本研究旨在探讨黑莓汁和三种浆果多酚化合物对人肝癌 HepG2 细胞和正常外周血单核细胞（PBMC）增殖和端粒酶活性的影响。
采用 MTT 和 TRAP 法分别测定细胞活力和端粒酶活性，定量 RT-PCR 法测定浆果对基因表达的影响。
黑莓、没食子酸和白藜芦醇均呈剂量依赖性抑制 HepG2 和 PBMC 细胞的增殖。与 PBMC 细胞相比，白藜芦醇对 HepG2 细胞活力的抑制作用更强，而没食子酸的效果则相同。黑莓、白藜芦醇和没食子酸均显著抑制 HepG2 细胞的端粒酶活性。黑莓的增殖抑制作用与细胞凋亡相关的 DNA 片段化有关。与白藜芦醇相比，没食子酸更能降低端粒酶活性，但花色苷在癌细胞中适度增加端粒酶活性。三种多酚均能诱导 PBMC 中端粒酶活性的增加。总体而言，克伦宁氯化物在 PBMC 中诱导端粒酶活性的效果比没食子酸和白藜芦醇更显著。与对照组相比，在处理过的 HepG2 细胞中，hTERT、hTR 和 Dnmts 的表达没有显著差异。然而，在处理过的细胞中，HDAC1 和 HDAC2 的表达显著下调，SIRT1 的表达显著上调。
这些数据表明，浆果的抗癌作用与抗端粒酶活性和 HDACs 表达的变化有关。数据还表明，浆果的抗端粒酶活性主要与其所含的没食子酸和白藜芦醇有关，而与花色苷含量无关。
