c-jun/AP-1 activation does not affect the antiproliferative activity of phenethyl isothiocyanate, a cruciferous vegetable-derived cancer chemopreventive agent

✍ Scribed by Song Yao; Yuesheng Zhang; Jun Li

• Book ID: 102502752
• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 278 KB
• Volume: 45
• Category: Article
• ISSN: 0899-1987
• DOI: 10.1002/mc.20206

✦ Synopsis

Abstract

Cruciferous vegetable‐derived isothiocyanates (ITCs) display potent cancer chemopreventive activity, but also markedly stimulate oncogenic activator protein 1 (AP‐1). AP‐1 is well known to promote cell survival and proliferation. We examined the impact of AP‐1 activation on antiproliferative activity of ITCs, using bladder cancer cells and phenethyl isothiocyanate (PEITC) as models. AP‐1 transactivation induced by PEITC was almost completely suppressed by a dominant‐negative c‐jun (TAM67). However, suppression of AP‐1 transactivation did not affect PEITC‐induced apoptosis or cell‐cycle arrest. Moreover, we previously showed that in response to ITC treatment c‐jun was predominantly stimulated among AP‐1 family members largely by c‐jun N‐terminal kinase (JNK) [Food Chem Toxicol 2005; 43: 1373–1380], but neither JNK inhibition nor forced expression of c‐jun altered the antiproliferative activity of PEITC. In addition, cyclin D1, which is considered as an AP‐1 target gene and promotes cell proliferation, was markedly elevated in PEITC‐treated cells. Unexpectedly, neither TAM67 or JNK inhibition, nor forced c‐jun expression had a significant impact on cyclin D1 induction by PEITC, indicating that c‐jun/AP‐1 does not play an important role in cyclin D1 induction by PEITC. In conclusion, despite the known role of c‐jun/AP‐1 as a stimulator of cell growth and proliferation, our data show that its activation does not diminish the antiproliferative activity of PEITC and is not responsible for cyclin D1 induction by PEITC. © 2006 Wiley‐Liss, Inc.