Antiproliferative mechanism of retinoid derivatives in ovarian cancer cells

Citation
Sj. Um et al., Antiproliferative mechanism of retinoid derivatives in ovarian cancer cells, CANCER LETT, 174(2), 2001, pp. 127-134
Citations number
41
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
CANCER LETTERS
ISSN journal
0304-3835 → ACNP
Volume
174
Issue
2
Year of publication
2001
Pages
127 - 134
Database
ISI
SICI code
0304-3835(200112)174:2<127:AMORDI>2.0.ZU;2-9
Abstract
Retinoid derivatives have been implicated for the growth regulation of ovar ian cancer cells. However, the molecular mechanisms are not yet fully defin ed. To dissect detailed mechanisms of each derivative, four ovarian cancer cells (A2774, PA-1, OVCAR-3, SKOV-3) were treated with all-trans retinoic a cid (ATRA), 9-cis retinoic acid (9-cis RA), 13-cis RA, or 4-hydroxyphenyl r etinamide (4-HPR). When treated with 1 muM, HPR inhibits most effectively t he growth of all four cells. Depending on cell types treated, IC50 values w ere 0.7-2.7 muM for 4-HPR, and 2.7-9.0 muM for other retinoid derivatives. DNA fragmentation assay indicated that the antiproliferative effect of HPR could be mediated by apoptosis. Transcription assays coupled with transient transfection in OVCAR-3 cells indicated that ATRA, 9-cis RA, and 13-cis RA were active for all RAR/RXR subtypes, whereas 4-HPR was only active for RA R gamma. However, 4-HPR exerted the strongest suppression on AP-1 (c-Jun) a ctivity. As expected from AP-1 data, in vitro invasion assays showed that H PR blocked effectively the migration of OVCAR-3 cells. Thus, 4-HPR showed n ot only more potent antiproliferative activity than any other retinoid deri vatives used, but also effectively inhibited the invasion, probably through the suppression of AP-1 activity. Taken together coupled with its selectiv e activity only for RAR gamma, these results suggest that 4-HPR could be le ss toxic, and very effective anticancer drugs for late stage ovarian cancer . (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.