All-trans-retinoic acid activates caspase-1 in a dose-dependent manner in cervical squamous carcinoma cells.
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.
Arany
Istvan
I
Departments of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555-1070, USA. AranyIstvan@uams.edu
Ember
Istvan A
IA
Tyring
Stephen K
SK
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D020170:Caspase 1 / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D050856:Interferon Regulatory Factor-1; D016376:Oligonucleotides, Antisense / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D016376:Oligonucleotides, Antisense; D010750:Phosphoproteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D014212:Tretinoin; D020170:Caspase 1