Saxatilin inhibits TNF-alpha-induced proliferation by suppressing AP-1-dependent IL-8 expression in the ovarian cancer cell line MDAH 2774.

Abstract

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.

• Authors: Dong Seok Kim, Yoon-Jung Jang, Ok-Hee Jeon, Doo-Sik Kim
• Journal: Molecular immunology (Mol Immunol) Vol. 44 Issue 6 Pg. 1409-16 (Feb 2007) ISSN: 0161-5890 [Print] England
• PMID: 16806476 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• CXCL8 protein, human
• Disintegrins
• Growth Inhibitors
• Interleukin-8
• Transcription Factor AP-1
• Tumor Necrosis Factor-alpha
• saxatilin

Topics

• Antineoplastic Agents (therapeutic use)
• Cell Line, Tumor
• Cell Proliferation
• Disintegrins (therapeutic use)
• Female
• Growth Inhibitors (therapeutic use)
• Humans
• Interleukin-8 (antagonists & inhibitors, biosynthesis, genetics)
• Ovarian Neoplasms (drug therapy, immunology)
• Transcription Factor AP-1 (antagonists & inhibitors, physiology)
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, physiology)