alexa Combination of tumor necrosis factor-alpha with sulindac augments its apoptotic potential and suppresses tumor growth of human carcinoma cells in nude mice.
Pathology

Pathology

Journal of Clinical & Experimental Pathology

Author(s): Yasui H, Adachi M, Imai K

Abstract Share this page

Abstract BACKGROUND: Resistance to apoptosis may be responsible for a principal mechanism by which cancer cells overcome anticancer therapies. Among antiapoptotic signals, the transcription factor, NF-kappaB, plays a pivotal role in the resistance because it is frequently activated in many primary carcinoma cells. However, NF-kappaB is also activated by several anticancer therapies, including tumor necrosis factor-alpha (TNF-alpha). The NF-kappaB-mediated survival signals are supposed to evade these therapies. Recently, a nonsteroidal antiinflammatory drug, sulindac, and its metabolites have been shown to inhibit the NF-kappaB pathway and to enhance TNF-alpha-mediated apoptosis in lung carcinoma cell lines. In the current study, the authors investigated whether sulindac can augment TNF-alpha-mediated apoptosis in other human carcinoma cells and whether it can be applied for in vivo clinical usage. METHODS: Human gastric MKN45 and cervical HeLa carcinoma cells were treated with sulindac and/or TNF-alpha. Proapoptotic effects of these agents were evaluated by trypan blue exclusion assay, DNA fragmentation, and caspase-3 activity. The effect of sulindac on NF-kappaB activation was evaluated by luciferase reporter and gel-shift assays. The suppressive effects of these reagents on the subcutaneous tumor growth of MKN45 cells were evaluated by measuring tumor size in nude mice. RESULTS: Sulindac inhibited TNF-alpha-mediated NF-kappaB activation and greatly sensitized MKN45 and HeLa cell lines to TNF-alpha. Moreover, in vivo tumor growth of MKN45 cells was inhibited most strongly by a combination of TNF-alpha with sulindac compared with TNF-alpha or sulindac alone. CONCLUSIONS: The current study data strongly suggest that combination therapy of TNF-alpha with sulindac may sensitize tumor cells to TNF-alpha and augment its proapoptotic potential. Therefore, in combination with sulindac, TNF-alpha may become a potentially useful anticancer agent to suppress tumor growth in a wide range of carcinomas. Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11210 This article was published in Cancer and referenced in Journal of Clinical & Experimental Pathology

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords