Resveratrol induces apoptosis through ROS-dependent mitochondria pathway in HT-29 human colorectal carcinoma cells.
trans-Resveratrol is a polyphenol found in blueberries, grapes, and wine with cancer chemopreventive properties. The low bioavailability of this compound enhances its concentration in the luminal content and becomes a potential chemopreventive agent against colon cancer. In the present study, the antiproliferative and pro-apoptotic effects on the human colorectal carcinoma HT-29 cells as well as the mechanisms underlying these effects were examined. Proliferation, cytotoxicity, and apoptosis were measured by fluorescence-based techniques. Studies of dose-dependent effects of trans-resveratrol showed antiproliferative activity with an EC 50 value of 78.9 +/- 5.4 microM. Caspase-3 was activated in a dose-dependent manner after incubation for 24 h giving an EC 50 value of 276.1 +/- 1.7 microM. Apoptosis was also confirmed with microscopic observation of changes in membrane permeability and detection of DNA fragmentation. The activity of trans-resveratrol on the mitochondria apoptosis pathway was evidenced by the production of superoxide anions in the mitochondria of cells undergoing apoptosis. In conclusion, trans-resveratrol inhibits cell proliferation without cytotoxicity and induces apoptosis in HT-29. Results of the present study provide evidence demonstrating the antitumor effect of trans-resveratrol via a ROS-dependent apoptosis pathway in colorectal carcinoma.
Department of Fisiologia, Facultat de Farmàcia, Universitat de Barcelona, Spain. mejuan@ub.edu
M Emília
ME
Juan
Uwe
U
Wenzel
Hannelore
H
Daniel
Joana M
JM
Planas
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000473:pathology* / Q000517:prevention & control; D053938:DNA Fragmentation; D019073:HT29 Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D017382:Reactive Oxygen Species; D013267:Stilbenes; D053148:Caspase 3; D000077185:Resveratrol