All-trans-retinoic acid activates caspase-1 in a dose-dependent manner in cervical squamous carcinoma cells

Abstract

Earlier we observed that all-trans-retinoic acid (ATRA) dose-dependently suppressed the growth of cervical carcinoma cells. Suppression of growth required sustained activation of interferon regulatory factor 1 (IRF-1), which was achieved by high-dose (10(-4) M), but not low-dose (10(-6) M), ATRA treatment. In this paper we examine the role of IRF-1 in cell death that accompanied the growth suppression in high-dose ATRA-treated cells. We found that high-dose, but not low-dose, ATRA treatment activated caspase-1 in those cervical carcinoma cells. Transient transfection of an antisense-IRF-1 construct diminished high-dose ATRA-mediated caspase-1 activation. On the other hand, ATRA was not able to induce caspase-1 expression in a STAT1 (signal transducer and activator of transcription 1) knockout cell line, but transient transfection of STAT1 restored it. These results suggested the importance of both IRF-1 and STAT1 in high-dose ATRA-induced activation of caspase-1. Our results might be useful in the treatment of retinoid-resistant cervical neoplasias.