Inhibition of Cellular Adhesion in Human Umbilical Vein Endothelial Cells by NF-κB Inhibitor DHMEQ Under Flow

Authors: Ohno, Osamu¹; Shima, Yutaka¹; Ikeda, Yasuo²; Sakurai, Kumi³; Watanabe, Kiyoaki³; Kawai, Yohko³; Umezawa, Kazuo¹

Source: Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics, Volume 15, Number 4, 2005 , pp. 189-197(9)

Publisher: Cognizant Communication Corporation

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Abstract:

We previously designed and synthesized DHMEQ as an inhibitor of NF-κB. In the present study, we looked into the effect of DHMEQ on the cell adhesion in human umbilical vein endothelial cells (HUVEC) under flow. We used freshly prepared HUVEC and human mononuclear cells throughout the experiment. DHMEQ inhibited TNF-α-, IL-1β-, and LPS-induced NF-κB activation in HUVEC. It also inhibited TNF-α-induced expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. DHMEQ also inhibited TNF-α-induced mononuclear cell–HUVEC adhesion. The effect of DHMEQ was more prominent when the cells were under shear stress. DHMEQ inhibited the adhesion between HUVEC and HT-29 colon cancer cells more clearly under the flow condition than under the static condition of the culture medium. These results suggest that DHMEQ, being a unique inhibitor of NF-κB, may be effective in suppressing atherosclerosis and metastasis by inhibiting the expression of adhesion molecules.

Keywords: DHMEQ; NF-κB; ICAM-1; VCAM-1; E-selectin; HUVEC

Document Type: Research article

Affiliations: 1: Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-0061, Japan 2: Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan 3: Department of Laboratory Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan

Publication date: 2005-04-01

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Formerly: Oncology Research Incorporating Anti-Cancer Drug Design
Oncology Research Featuring Preclinical and Clincal Cancer Therapeutics publishes research of the highest quality that contributes to an understanding of cancer in areas of molecular biology, cell biology, biochemistry, biophysics, genetics, biology, endocrinology, and immunology, as well as studies on the mechanism of action of carcinogens and therapeutic agents, reports dealing with cancer prevention and epidemiology, and clinical trials delineating effective new therapeutic regimens.

Inhibition of Cellular Adhesion in Human Umbilical Vein Endothelial Cells by NF-κB Inhibitor DHMEQ Under Flow

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