J Korean Cancer Assoc.  2000 Dec;32(6):1043-1049.

Growth Regulation of Ovarian Cancer Cells through the Inactivation of AP-1 by Retinoid Derivatives

Affiliations
  • 1Departments of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
  • 2Departments of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul, Korea.
  • 3Department of Bioscience and Biotechnology, Institute of Bioscience, Sejong University, Seoul, Korea. E-mail: umsj@sejong.ac.kr

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.

Keyword

Ovarian cancer cell lines; Retinoic acid; 4-Hydroxyphenyl retinamide; Retinoic acid receptor; Retinoid X receptor; Activation protein-1

MeSH Terms

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
Fenretinide
Receptors, Retinoic Acid
Retinoid X Receptors
Retinoids
Transcription Factor AP-1
Transcription Factors
Tretinoin
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