Apoptosis effects of Xrel3 c-Rel/Nuclear Factor-kappa B homolog in human cervical cancer cells.
Cervical cancer is considered a common yet preventable cause of death in women. In this report, we studied the role of the NF-kappaB gene family in HeLa human cervical cancer cells, using the Xrel3 c-Rel homologue of Xenopus laevis. The expression of Xrel3/c-Rel slowed cell growth 6-fold, consistent with an upregulated expression of the cell cycle inhibitor p21. The activated PARP apoptosis effector was significantly increased (P<0.01). Based on cell viability assays Xrel3 provided an anti-apoptotic effect in 1 microM cisplatin, and this was associated with significantly lower levels of the apoptotic proteins Bax and MDM-2 (P<0.05). Furthermore, there was a 3-fold drop in the level of the tumor suppressor protein p53. In 5 microM cisplatin, expression of HeLa Xrel3 enhanced apoptosis by significantly increasing the expression of the apoptotic proteins Bax and MDM-2 (P<0.05). However, the tumor suppressor protein p53 showed a significant decrease (P<0.05) relative to the control. Thus, c-Rel/NF-kappaB may potentially be of clinical significance, especially in tumors exhibiting resistance to high-level chemotherapy.
Shehata
Marlene
M
Division of Basic Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NF A1B 3V6, Canada. mshehata@ottawaheart.ca
Shehata
Marian
M
Shehata
Fady
F
Pater
Alan
A
D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D049109:Cell Proliferation; D002945:Cisplatin / Q000494:pharmacology; D017124:Conserved Sequence; D004318:Doxycycline / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020573:Genes, rel / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D017385:Sequence Homology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014981:Xenopus; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*
D016328:NF-kappa B; D012333:RNA, Messenger; C112657:TP53 protein, Xenopus; D014157:Transcription Factors; D029867:Xenopus Proteins; D011065:Poly(ADP-ribose) Polymerases; D004318:Doxycycline; D002945:Cisplatin