Inhibition of gastric cancer cell proliferation by resveratrol: role of nitric oxide.
Resveratrol is a dietary phytochemical that has been shown to inhibit proliferation of a number of cell lines, and it behaves as a chemopreventive agent in assays that measure the three stages of carcinogenesis. We tested for its chemopreventive potential against gastric cancer by determining its interaction with signaling mechanisms that contribute to the proliferation of transformed cells. Low levels of exogenous reactive oxygen (H(2)O(2)) stimulated [(3)H]thymidine uptake in human gastric adenocarcinoma SNU-1 cells, whereas resveratrol suppressed both synthesis of DNA and generation of endogenous O(2)(-) but stimulated nitric oxide (NO) synthase (NOS) activity. To address the role of NO in the antioxidant action of resveratrol, we measured the effect of sodium nitroprusside (SNP), an NO donor, on O(2)(-) generation and on [(3)H]thymidine incorporation. SNP inhibited DNA synthesis and suppressed ionomycin-stimulated O(2)(-) generation in a concentration-dependent manner. Our results revealed that the antioxidant action of resveratrol toward gastric adenocarcinoma SNU-1 cells may reside in its ability to stimulate NOS to produce low levels of NO, which, in turn, exert antioxidant action. Resveratrol-induced inhibition of SNU-1 proliferation may be partly dependent on NO formation, and we hypothesize that resveratrol exerts its antiproliferative action by interfering with the action of endogenously produced reactive oxygen. These data are supportive of the action of NO against reactive oxygen and suggest that a resveratrol-rich diet may be chemopreventive against gastric cancer.
Holian
Oksana
O
Department of Medicine, Division of Gastroenterology, Cook County Hospital, Chicago, Illinois 60612, USA. oholian@aol.com
Wahid
Shahid
S
Atten
Mary Jo
MJ
Attar
Bashar M
BM
D000230:Adenocarcinoma; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D009249:NADP / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013274:Stomach Neoplasms; D013481:Superoxides / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D007476:Ionophores; D020030:Nitric Oxide Donors; D016877:Oxidants; D017382:Reactive Oxygen Species; D013267:Stilbenes; D013481:Superoxides; D009599:Nitroprusside; D009569:Nitric Oxide; D009249:NADP; D015759:Ionomycin; D004247:DNA; D006861:Hydrogen Peroxide; D019001:Nitric Oxide Synthase; D011493:Protein Kinase C; D000077185:Resveratrol