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.
Kim
Dong Seok
DS
Department of Biochemistry, College of Science, Yonsei University, 134 Sinchon-dong, Seodaemun-gu, Seoul 120-749, Republic of Korea.
Jang
Yoon-Jung
YJ
Jeon
Ok-Hee
OH
Kim
Doo-Sik
DS
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019483:Disintegrins / Q000627:therapeutic use*; D005260:Female; D006131:Growth Inhibitors / Q000627:therapeutic use*; D006801:Humans; D016209:Interleukin-8 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000276:immunology; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors* / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000502:physiology
D000970:Antineoplastic Agents; C508606:CXCL8 protein, human; D019483:Disintegrins; D006131:Growth Inhibitors; D016209:Interleukin-8; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; C459080:saxatilin