Resveratrol-induced inactivation of human gastric adenocarcinoma cells through a protein kinase C-mediated mechanism.
Resveratrol, a polyphenolic phytochemical present in berries, grapes, and wine, has emerged as a promising chemopreventive candidate. Because there is scant information regarding natural agents that prevent, suppress, or reverse gastric carcinogenesis, the aim of the present study was to determine the chemopreventive potential of resveratrol against gastric cancer by investigating cellular and molecular events associated with resveratrol treatment of human gastric adenocarcinoma cells. We determined the action of resveratrol on cellular function and cellular integrity by measuring DNA synthesis, cellular proliferation, cell cycle distribution, cytolysis, apoptosis, and phosphotransferase activities of two key signaling enzymes, protein kinase C (PKC) and mitogen-activated protein kinases (ERK1/ERK2), in human gastric adenocarcinoma KATO-III and RF-1 cells. Resveratrol inhibited [3H]thymidine incorporation into cellular DNA of normally proliferating KATO-III cells and of RF-1 cells whose proliferation was stimulated with carcinogenic nitrosamines. Treatment with resveratrol arrested KATO-III cells in the G(0)/G(1) phase of the cell cycle and eventually induced apoptotic cell death, but had a minimal effect on cell lysis. Resveratrol treatment had no effect on ERK1/ERK2 activity but significantly inhibited PKC activity of KATO-III cells and of human recombinant PKCalpha. Results indicate that resveratrol has potential as a chemopreventive agent against gastric cancer because it exerts an overall deactivating effect on human gastric adenocarcinoma cells. Resveratrol-induced inhibition of PKC activity and of PKCalpha, without any change in ERK1/ERK2 activity, suggests that resveratrol utilizes a PKC-mediated mechanism to deactivate gastric adenocarcinoma cells.
Atten
M J
MJ
Department of Medicine, Division of Gastroenterology, Cook County Hospital and Hektoen Institute for Medical Research, 627 S. Wood St., Room 765, Chicago, IL 60612, USA.
Attar
B M
BM
Milson
T
T
Holian
O
O
D000230:Adenocarcinoma; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000187:drug effects*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013274:Stomach Neoplasms; D014407:Tumor Cells, Cultured
D016588:Anticarcinogenic Agents; D004273:DNA, Neoplasm; D013267:Stilbenes; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D000077185:Resveratrol