Digalloylresveratrol, a new phenolic acid derivative induces apoptosis and cell cycle arrest in human HT-29 colon cancer cells.
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| Abstract |
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 microM 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 (14)C-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.
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| Authors | Astrid Bernhaus, Monika Fritzer-Szekeres, Michael Grusch, Philipp Saiko, Georg Krupitza, Somepalli Venkateswarlu, Golakoti Trimurtulu, Walter Jaeger, Thomas Szekeres |
| Journal | Cancer letters (Cancer Lett) Vol. 274 Issue 2 Pg. 299-304 (Feb 18 2009) ISSN: 1872-7980 [Electronic] Ireland |
| PMID | 18952370 (Publication Type: Journal Article) |
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