Inhibitory effects of γ-tocotrienol on invasion and metastasis of human gastric adenocarcinoma SGC-7901 cells☆☆☆
Received 18 July 2008; received in revised form 5 October 2008; accepted 24 November 2008. published online 06 February 2009.
Abstract
Natural vitamin E is a mixture of two classes of compounds, tocopherols and tocotrienols. Recent research has revealed that tocotrienols, especially γ-tocotrienol, exhibit not only the same antioxidant ability as tocopherols, but also remarkable anticancer capacity in cancer cell lines. In this study, the invasion and metastatic capacities of gastric adenocarcinoma SGC-7901 cells and the correlation with antimetastasis mechanisms induced by γ-tocotrienol were explored. The results showed the inhibitory effects of γ-tocotrienol at doses of 15, 30, 45 and 60 μmol/L for 48 h on cell migration and cell matrigel invasion; activities of matrix metalloproteinase (MMPs) increased in SGC-7901 cells when compared to the control group (P<.05 or P<.01). An increasing trend in the chemotactic responses to fibronectin (FN) in SGC-7901 cells was found in the γ-tocotrienol treatments. SGC-7901 cell attachment decreased in the γ-tocotrienol-treated groups in comparison with the control group (P<.01). The mRNA expressions of MMP-2 and MMP-9 showed that γ-tocotrienol significantly reduced the matrigel invasion capability through down-regulation of the mRNA expressions of MMP-2 and MMP-9 (P<.01), and up-regulation of tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 in SGC-7901 cells by treatment with γ-tocotrienol for 48 h (P<.05). γ-Tocotrienol also significantly increased the mRNA expression of nm23-H1 in SGC-7901 cells (P<.01). These findings suggest a potential mechanism of γ-tocotrienol-mediated antitumor metastasis activity and indicate the role of vitamin E as potential chemopreventative agents against gastric cancer.
aDepartment of Nutrition and Food Hygiene, Public Health School, Harbin Medical University, NanGang District, Harbin, Heilongjiang Province 150086, People's Republic of China
bDepartment of Clinic Nutrition, The First Clinical College of Harbin Medical University, NanGang District, Harbin 150001, People's Republic of China
cAgricultural Research Station, Virginia State University, Petersburg, VA 23836, USA
dCancer Research Institute, Harbin Medical University, Harbin 150081, People's Republic of China
☆ This project is supported by the National Natural Science Foundation of China (No. 30471444), the Innovative Foundation of Harbin Medical University (No. HCXB2008007) and the Innovative Foundation of Heilongjiang Province (No.YJSCX2008-118HLJ).
☆☆ There are no conflicts of interest in this manuscript.
1 Co-first author: contributed equally to this work.