Cited 30 time in
- Title
- Mitomycin C induces apoptosis via Fas/FasL dependent pathway and suppression of IL-18 in cervical carcinoma cells
- Author(s)
- Yun Hee Kang; Kyung Ae Lee; Chun Jeih Ryu; Hee Gu Lee; J S Lim; S N Park; S G Paik; Do Young Yoon
- Bibliographic Citation
- Cancer Letters, vol. 237, no. 1, pp. 33-44
- Publication Year
- 2006
- Abstract
- Mitomycin C (MMC) is used fairly widely as an anticancer drug, as it possesses mechanisms of action which are preferable to other chemotherapeutic compounds, including cisplatin, docetaxel, and lovastatin. In the previous study, we established the RSV-luc promoter analysis system, which is used to screen drugs against cervical carcinomas caused by HPV infection. We then demonstrated the repression of HPV E6-activated RSV promoter activity by anticancer agents such as carboplatin (CA), cisplatin (CIS), and MMC. In these studies, we focused on the investigation of apoptotic mechanisms in MMC-treated cervical carcinoma cell lines, most notably SiHa/pRSV-luc (KCTC 0427BP) and SiHa. DNA fragmentation assays and TUNEL staining revealed that MMC and CIS, but not CA, resulted in apoptosis. MMC treatment induced a reduction in the expressions of the E6 oncogene and IL-18, in a p53-independent manner. MMC also increased FasL expression and induced the processing of caspases-8 and -3. Our results indicated that MMC induced apoptosis in SiHa/pRSV-luc and SiHa cells via caspase-8 and -3 processing, in a Fas/FasL-dependent manner. MMC also suppressed the expression of IL-18 in the same cells. MMC also down-regulated IκB expression, and up-regulated p65 expression. These results suggest that MMC induces apoptosis, not only through caspase-8 and -3 dependent Fas/FasL pathway, but also via the regulation of NF-κB activity and IL-18 expression.
- Keyword
- ApoptosisCaspase-8Cervical carcinoma cellsFasLInterleukin-18Mitomycin C
- ISSN
- 0304-3835
- Publisher
- Elsevier
- DOI
- http://dx.doi.org/10.1016/j.canlet.2005.05.043
- Type
- Article
- Appears in Collections:
- Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
- Files in This Item:
Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.