PMID- 16806476 OWN - NLM STAT- MEDLINE DCOM- 20070305 LR - 20190816 IS - 0161-5890 (Print) IS - 0161-5890 (Linking) VI - 44 IP - 6 DP - 2007 Feb TI - Saxatilin inhibits TNF-alpha-induced proliferation by suppressing AP-1-dependent IL-8 expression in the ovarian cancer cell line MDAH 2774. PG - 1409-16 AB - Tumor necrosis factor-alpha (TNF-alpha)-induced proliferation of cancer cell line MDAH 2774 was significantly suppressed by treating the cells with saxatilin, a snake venom disintegrin. The suppressed proliferation was found to be associated with the level of interleukin-8 (IL-8) expression in the cells. TNF-alpha-induced IL-8 promoter activation that is inhibited by saxatilin treatment was dependent on activating protein-1 (AP-1) instead of nuclear factor-kappa B (NF-kappaB). Coexpression of dominant negative p38 (DN-p38) suggested that p38 is involved in the IL-8 promoter activity which is regulated by saxatilin or TNF-alpha. Experimental evidence clearly indicated that saxatilin inhibits TNF-alpha-induced proliferation of the ovarian cancer cells by suppressing IL-8 expression in AP-1-dependent manner. FAU - Kim, Dong Seok AU - Kim DS AD - Department of Biochemistry, College of Science, Yonsei University, 134 Sinchon-dong, Seodaemun-gu, Seoul 120-749, Republic of Korea. FAU - Jang, Yoon-Jung AU - Jang YJ FAU - Jeon, Ok-Hee AU - Jeon OH FAU - Kim, Doo-Sik AU - Kim DS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060627 PL - England TA - Mol Immunol JT - Molecular immunology JID - 7905289 RN - 0 (Antineoplastic Agents) RN - 0 (CXCL8 protein, human) RN - 0 (Disintegrins) RN - 0 (Growth Inhibitors) RN - 0 (Interleukin-8) RN - 0 (Transcription Factor AP-1) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (saxatilin) SB - IM MH - Antineoplastic Agents/*therapeutic use MH - Cell Line, Tumor MH - *Cell Proliferation MH - Disintegrins/*therapeutic use MH - Female MH - Growth Inhibitors/*therapeutic use MH - Humans MH - Interleukin-8/*antagonists & inhibitors/biosynthesis/genetics MH - Ovarian Neoplasms/*drug therapy/immunology MH - Transcription Factor AP-1/*antagonists & inhibitors/physiology MH - Tumor Necrosis Factor-alpha/*antagonists & inhibitors/physiology EDAT- 2006/06/30 09:00 MHDA- 2007/03/06 09:00 CRDT- 2006/06/30 09:00 PHST- 2006/02/27 00:00 [received] PHST- 2006/04/29 00:00 [revised] PHST- 2006/05/01 00:00 [accepted] PHST- 2006/06/30 09:00 [pubmed] PHST- 2007/03/06 09:00 [medline] PHST- 2006/06/30 09:00 [entrez] AID - S0161-5890(06)00177-5 [pii] AID - 10.1016/j.molimm.2006.05.001 [doi] PST - ppublish SO - Mol Immunol. 2007 Feb;44(6):1409-16. doi: 10.1016/j.molimm.2006.05.001. Epub 2006 Jun 27.