J. Cancer Mol. 2: 199-205, 2006

[Research Paper]

Sesamin Inhibits Vascular Endothelial Cell Growth and Angiogenic Activity of Lung Adenocarcinoma Cells

Shiow-Chwen Tsai, Ya-Chen Liu, Chung-Pin Li, Tze-Sing Huang, and Chun-Chung Lee

Department of Medical Education and Research, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, ROC [S.-C. Tsai, Y.-C. Liu]; Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital and National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC [C.-P. Li]; National Institute of Cancer Research, National Health Research Institutes, Taipei, Taiwan, ROC [T.-S. Huang, C.-C. Lee]

Abstract:

AIM: Sesamin has been indicated to have antihypertensive, antioxidative and antiinflammatory properties.  Angiogenesis is the subsequent event of inflammation during wound healing and tumor progression.  To investigate whether or not sesamin exerts anti-angiogenic activity, we examined the effects of sesamin on vascular endothelial cells and on the angiogenic activity of cancer cells.

METHODS: Human umbilical vein endothelial cells (HUVECs) were isolated and cultivated for the treatments with sesamin.  Cell viabilities and growth curves were determined by microculture tetrazolium test and trypan blue exclusion assay.  In vitro wound healing and Matrigel invasion assays were performed to determine the migration and invasion abilities of HUVECs.  The level of endothelial cell capillary tube and network formation was used to evaluate the angiogenic activity of human lung adenocarcinoma CL1-5 cells.  Northern blot analyses were used to detect matrix metalloproteinase-2 (MMP-2) and VEGF mRNA levels in HUVECs and CL1-5 cells, respectively.  Western blot was used to estimate the VEGF protein expression in CL1-5 cells and gelatinase zymography was performed to detect the MMP-2 levels secreted from HUVECs.

RESULTS: Sesamin inhibited the growth of HUVECs without causing significant cytotoxicity.  Sesamin inhibited HUVECs migrating through the matrigel and inhibited their MMP-2 gene expression and enzyme level.  Additionally, we found that sesamin inhibited VEGF-induced HUVEC migration by using the wound healing assay.  Sesamin inhibited the VEGF expression in invasive CL1-5 cells.  The culture media collected from sesamin-pretreated CL1-5 cells were lost the activity to induce the formation of endothelial cell capillary tube and network if compared with the media from untreated CL1-5 cells.

CONCLUSION:  Sesamin exhibits the anti-angiogenic activity and is potential for preventing tumor angiogenesis.

Received 9/29/06; Revised 10/16/06; Accepted 10/16/06.

¹Correspondence: Dr. Chun-Chung Lee, National Institute of Cancer Research, National Health Research Institutes, 7F, No. 161, Min-Chuan East Road Sec. 6, Taipei 114, Taiwan, Republic of China. Phone: 886-2-2653 4401 ext 25111. Fax: 886-2-2792 9654. E-mail: cclee@nhri.org.tw

²Abbreviations: ROS, reactive oxygen species; MAPK, mitogen-activated protein kinase; IL, interleukin; VEGF, vascular endothelial growth factor; FGF, fibroblast growth factor; TNF-a, tumor necrosis factor-a; TGF-b, transforming growth factor-b; MMP, matrix metalloproteinase; uPA, urokinase-type plasminogen activator; HUVECs, human umbilical vein endothelial cells; MTT, microculture tetrazolium test; HIF-1, hypoxia-inducible factor-1.