N-hydroxy-7-(2-naphthylthio) heptanomide (HNHA), histone deacetylase inhibitors, suppresses COX-2 expression in colon cancer

Abstract

[한글]

[영문]

Cyclooxygenase-2 (COX-2) plays important roles in cell adhesion, apoptosis, and angiogenesis, and is essential for tumor angiogenesis. Levels of COX-2 expression are low in normal cells, but very high level in human and animal colorectal tumors.Histone deacetylase (HDAC) plays a crucial role in carcinogenesis1 and is over-expressed in several tumor cells2. The histone deacetylase inhibitor N-hydroxy-7-(2-naphthylthio) heptanomide (HNHA) is a new anti-angiogenesis drug, and has been shown to inhibit COX-2 expression in colon cancer. Here, we confirm that HNHA decreases COX-2 expression in colon cancer, similar to COX-2 inhibitors such as Celecoxib and Rofecoxib. Moreover, hypoxia inducible factor-1α (HIF-1α), and tumor necrosis factor-α (TNF-α) are involved in COX-2 expression and their expression is also decreased by HNHA in colon cancer. The effect of HNHA on tumor growth was examined in a human colon cancer tumor model and investigated by western blot, immunohistochemistry, and FACS analysis.