KO-202125, a sauristolactam derivate, induces apoptosis to prevent KB human oral squamous carcinoma cells through inhibition of cyclooxygenase-2 expression.

Abstract

In a previous study, we demonstrated that cyclooxygenase-2 (COX-2) is overexpressed in Korean patients having oral cancer. The goal of this study was to study whether KO-202125 (KO), a sauristolactam derivative in KB human oral squamous carcinoma cells, inhibits the activity of COX-2 enzyme and induces apoptotic cell death. In this study, it was shown that KO inhibited COX-2 mRNA and protein and its catalytic activity (prostaglandin E2), but not COX-1. The antiproliferative effect of KO on KB cells was also examined. The results showed that KO significantly decreased the number of viable cells and showed morphological changes in a concentration-dependent manner. The decrease in cell number was associated with apoptotic cell death evidenced by cleaved poly ADP ribose polymerase (PARP), nuclear fragmentation, sub-G1 population and annexin V positivity. Interestingly, KO is more potent than celecoxib, which is a well-known selective COX-2 inhibitor, although more studies are needed to prove it. Altogether, these results show that KO can act as a potent antioral cancer drug candidate by regulating COX-2 activity.

• Authors: Dae-Ho Leem, Kyeong-Hee Choi, Hye-Suk Han, Jun-Hee Kim, Ji-Ae Shin, Eun-Sun Choi, Jung-Hyun Shim, Gu Kong, Yong-Ki Min, Jeong-Seok Nam, Seung Hyun Oh, Kyoung-A Kim, Ki Han Kwon, Nam-Pyo Cho, Sung-Dae Cho
• Journal: European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) (Eur J Cancer Prev) Vol. 19 Issue 1 Pg. 23-30 (Jan 2010) ISSN: 1473-5709 [Electronic] England
• PMID: 19910795 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alkaloids
• Antineoplastic Agents
• Isoindoles
• KO 202125
• Lactams
• Phenanthrenes
• Pyrazoles
• Sulfonamides
• sauristolactam
• Cyclooxygenase 2
• Celecoxib

Topics

• Alkaloids (chemistry, pharmacology)
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Carcinoma, Squamous Cell (genetics, metabolism, pathology)
• Celecoxib
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Cyclooxygenase 2 (genetics, metabolism)
• Down-Regulation (drug effects)
• Drug Evaluation, Preclinical
• Gene Expression Regulation, Enzymologic (drug effects)
• Humans
• Isoindoles (pharmacology)
• KB Cells
• Lactams (chemistry, pharmacology)
• Mouth Neoplasms (genetics, metabolism, pathology)
• Phenanthrenes (chemistry, pharmacology)
• Pyrazoles (pharmacology)
• Sulfonamides (pharmacology)