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

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.