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KMID : 1140120060110010065
Cancer Prevention Research
2006 Volume.11 No. 1 p.65 ~ p.72
The Inhibitory Effect of Resveratrol on the Growth of Human Pancreatic Cancer Cell Line in Vitro
Lee Jee-Young

Eo Wan-Kyu
Kim Boh-Kyung
Jung Keun-Ok
Koo Ja-Young
Abstract
Resveratrol (3,5,4¡¯-trihydroxystilbene), a phytoalexin, is emerging as a natural compound with anti- oxidative, anti-angiogenic and anti-carcinogenic activity and anti-inflammatory effects in animals, but only a small number of studies were done on its anti-proliferative effects, especially in pancreatic cancer. In the present study the effects of resveratrol on the growth of human pancreatic cancer cell line, capan-1 cells were examined and the combined effects with 5-fluorouracil (5-FU) were also studied. Cell cycle distribution and apoptosis induction were evaluated to determine the mechanisms for the inhibitory effects of resveratrol. The growth of capan-1 cells was examined by counting cell number on two and four days treatment with 1, 2.5, 5, 7.5, 10, 25 and 50¥ìM resveratrol, and 0.1 and 0.3¥ìg/ml 5-FU, after plating capan-1 cells into 35 mm2 plastic dishes at a density of 10 104 cells/dish. The reversibility of the effects of resveratrol was examined on one day to seven days treatment with 7.5¥ìM resveratrol after seeding 2 104 cells/dish. To examine the mechanisms for the inhibitory effects of resveratrol, cell cycle analysis was done on the cells after four days treatment with 10, 50, and 100¥ìM resveratrol. Resveratrol significantly inhibited the growth of capan-1 cells in a dose-dependent fashion (p£¼0.05). After removal of the resveratrol from the media, the suppressive effect of resveratrol on cell proliferation did not returned to normal, and cell count was significantly lower than that of control (p£¼0.05). Resveratrol enhanced the inhibitory effect of 5-FU on capan-1 cells. 4) The cells accumulated at the S and G0/G1 transition of the cell cycle. Resveratrol induced apoptosis of cells and it was correlated with the concentration of resveratrol. Resveratrol significantly inhibited the growth of capan-1 cells in a dose- dependent fashion and its inhibitory effect was irreversible. The inhibitory effect of resveratrol on the proliferation of capan-1 cells may be derived from inhibition of progression from S to G2/M of the cell cycle, and from the apoptosis that is proportional to the concentration of resveratrol. Enhanced inhibitory effect of 5-FU on capan-1 cells by adding resveratrol may help avoid toxic side effect of 5-FU by decreasing its dose. In vivo study is needed.
KEYWORD
Resveratrol, 5-FU, Pancreatic cancer cell, Capan-1 cell, Cell culture
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