Growth Regulation of Ovarian Cancer Cells through the Inactivation of AP-1 by Retinoid Derivatives.
- Author:
Young Me KOH
1
;
Jong Sup PARK
;
Sung Eun NAMKOONG
;
So Young LEE
;
Soo A KIM
;
Kyong Ja HONG
;
Soo Jong UM
Author Information
1. Departments of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Ovarian cancer cell lines;
Retinoic acid;
4-Hydroxyphenyl retinamide;
Retinoic acid receptor;
Retinoid X receptor;
Activation protein-1
- MeSH:
Animals;
Cats;
Cell Line;
Cell Proliferation;
Enzyme-Linked Immunosorbent Assay;
Fenretinide;
Ovarian Neoplasms*;
Receptors, Retinoic Acid;
Retinoid X Receptors;
Retinoids;
Transcription Factor AP-1*;
Transcription Factors;
Transfection;
Tretinoin
- From:Journal of the Korean Cancer Association
2000;32(6):1043-1049
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
PURPOSE: The growth regulatory effect of retinoid derivatives could be mediated by the transcriptional inactivation of AP-1 oncogenic transcription factor. By using ovarian cancer cell lines we were to investigate the cross-regulation mechanism between retinoids and AP-1. MATERIALS AND METHODS: Cell proliferation assays were performed in 4 ovarian cancer cells (A2774, PA-1, OVCAR-3, SKOV-3) by increasing the concentrations of all-trans retinoic acid (ATRA), 9-cis retinoic acid (9RA), 13-cis RA (13RA), 4-hydroxyphenyl retinamide (4-HPR). Transient transfection and CAT ELISA were done to determine the selective activity of each retinoid on the RAR (alpha, beta, gamma), RXR (alpha, beta, gamma). and the negative activity on AP-1 (c-Jun). RESULTS: Antiproliferative effect of 4-HPR (IC50; 0.7~2.7 micrometer) was more potent than those of other retinoid derivatives (IC50; 2.7~9.0 micrometer). To assess the anticancer mechanism, we examined the effect of 4-HPR on the transriptional activity of retinoic acid receptors (RAR/RXR) and of c-jun. Contrary to other retinoid derivatives that are active for RAR and RXR with some different levels, 4-HPR showed weak activity only for RARgamma. However, 4-HPR exerted the strongest suppression on AP-1 (c-Jun) activity. CONCLUSION: Based on our results showing much 4-HPR's potent antiproliferative activity coupled with the most effectively inhibiting activity on AP-1 and minimum activity on RA receptor (selective for RARgamma) than other retinoid derivatives, we suggest that 4-HPR may be a novel, and very effective anticancer drugs for ovarian cancer.
