The apoptotic effect of intercalating agents on HPV-negative cervical cancer C-33A cells.
Cervical cancer is one of the leading causes of female cancer death worldwide with about 500,000 deaths per year. Both mitomycin C and cisplatin are alkylating agents, which bind and intercalate DNA, and thus used as anti-cancer drugs. In these studies, we focused on investigating the apoptotic effects of intercalating agents on HPV-negative cervical cancer C-33A cells. Accordingly, C-33A cells were treated with carboplatin, mitomycin C or cisplatin. Cell cycle analysis revealed that treatment with mitomycin C and cisplatin but not with carboplatin resulted in apoptosis. Both mitomycin C and cisplatin induced apoptosis in C-33A cells via caspase-8 and -3 processing in a Fas/FasL-dependent manner and also suppressed IL-18 expression, while they down-regulated IkappaB expression and up-regulated p65 expression. These results suggest that both mitomycin C and cisplatin induce apoptosis, not only via the caspase-8 and -3 dependent Fas/FasL pathway, but also via the regulation of NF-kappaB activity and IL-18 expression in HPV-negative cervical cancer C-33A cells.
Kang
Yun Hee
YH
Department of Bioscience and Biotechnology, Konkuk University, Seoul, South Korea.
Lee
Kyung-Ac
KA
Yang
Young
Y
Kim
Soo-Hyun
SH
Kim
Joo Hwan
JH
Park
Sue Nie
SN
Paik
Sang-Gi
SG
Yoon
Do-Young
DY
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D016190:Carboplatin / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D053222:Fas Ligand Protein / Q000378:metabolism; D005260:Female; D006801:Humans; D007364:Intercalating Agents / Q000494:pharmacology*; D020382:Interleukin-18 / Q000378:metabolism; D016685:Mitomycin / Q000494:pharmacology; D027383:Papillomaviridae; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D019014:fas Receptor / Q000378:metabolism
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D007364:Intercalating Agents; D020382:Interleukin-18; D019014:fas Receptor; D016685:Mitomycin; D016190:Carboplatin; D020169:Caspases; D002945:Cisplatin