Digalloylresveratrol, a new phenolic acid derivative induces apoptosis and cell cycle arrest in human HT-29 colon cancer cells

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• 作者：Astrid Bernhaus ; Monika Fritzer-Szekeres ; Michael Grusch ; Philipp Saiko ; Georg Krupitza ; Somepalli Venkateswarlu ; Golakoti Trimurtulu ; Walter Jaeger ; Thomas Szekeres
• 关键词：Resveratrol ; Gallic acid ; HT-29 cells ; Apoptosis ; Ribonucleotide reductase ; Cell cycle
• 刊名：Cancer Letters
• 出版年：2009
• 出版时间：18 February 2009
• 年：2009
• 卷：274
• 期：2
• 页码：299-304
• 全文大小：283 K

文摘

Digalloylresveratrol (DIG) is a new synthetic ester of the naturally occurring polyhydroxyphenolic substances gallic acid and resveratrol which both exert anti-cancer activity in a number of tumor cell lines. The aim of the study was to identify the biochemical effects of DIG in HT-29 human colon cancer cells. DIG induced dose-dependently apoptosis after treatment for 72 h (40 μM DIG caused apoptosis in 45 % of cells).

DIG led to a substantial imbalance of deoxyribonucleoside triphosphates (dNTPs), the products of the enzyme ribonucleotide reductase (RR) and directly inhibited RR as it significantly reduced the incorporation of ¹⁴C-labeled cytidine into the DNA of tumor cells. Furthermore, DIG affected the cell division and inhibited the transition from S to G2/M phase of the cell cycle. In contrast to resveratrol or gallic acid, DIG did not inhibit cyclooxygenases I and II. When HT-29 cells were simultaneously treated with DIG and 5-FU, the standard chemotherapeutic substance for colon cancer, additive growth inhibitory effects could be observed. With respect to the various biochemical and anti-proliferative effects of DIG in HT-29 cells, we regard DIG as a potential candidate for future treatment options of colon cancer and conclude that further preclinical and in vivo studies are warranted.