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Title   AP-1 의 불활성화에 의한 Retinoid 유도체의 난소암 성장 억제 ( Growth Regulation of Ovarian Cancer Cells through the Inactivation of AP-1 by Retinoid Derivatives )
Publicationinfo   2000 Jan; 032(06): 1043-1050.
Key_word   Ovarian cancer cell lines , Retinoic acid , 4-Hydroxyphenyl retinamide , Retinoic acid receptor , Retinoid X receptor, Activation protein-1
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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 (α, β, γ), RXR (α, β, γ). and the negative activity on AP-1 (c-Jun). Results: Antiproliferative effect of 4-HPR ( IC50, 0.7~2.7 pμ) was more potent than those of other retinoid derivatives (ICw, 2.7-9.0 pM). 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 RAR y. However, 4-HPR exerted the strongest suppression on AP-1 (c-Jun) activity. Conclusion: Based on our results showing much 4-HPRs potent antiproliferative activity coupled with the most effectively inhibiting activity on AP-1 and minimum activity on RA receptor (selective for RAR y) than other retinoid derivatives, we suggest that 4-HPR may be a novel, and very effective anticancer drugs for ovarian cancer.
저 자   남궁성은(Sung Eun Namkoong),엄수종(Soo Jong Um),박종섭(Jong Sup Park),고영미(Young Me Koh),이소영(Sung Eun Nam koong),김수아(Soo A Kim),홍경자(Kyong Ja Hong)