J. Cancer Mol. 2: 199-205,
Sesamin Inhibits Vascular Endothelial Cell Growth and Angiogenic
Activity of Lung Adenocarcinoma Cells
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]
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.
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
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.
Sesamin exhibits the anti-angiogenic activity and is potential for
preventing tumor angiogenesis.
angiogenesis; MMP-2; VEGF)
9/29/06; Revised 10/16/06; Accepted 10/16/06.
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: firstname.lastname@example.org
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;
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.