Iron has a I"ole not on ly in the sy nthesis of hemoglobin but also in cell growth, including tumor development and progression. Excess iron aids tumor development by catalyzin g t he production of oxygen radicals that may be proximate carcinogens and by being a limiting nutrient to the growth and repli cation of cancer cells . Iron chelators have been shown to inhibit the growth and/or induce thc apoptosis of malignant cell lines from leukemia‘ neuroblastoma, melanoma. hepatoma, Kaposi's sarcoma, and cervical cancer. To ow' knowledge, iron chelating agents man ifesting anti-oral cancer effects has not been reported so fa r, and there a re no comparative studies on the elTects of c1esferrioxamine(DFO) on skin keratinocytes vs oral keratinocytes and on imm o J떠li zed cells vs oral cancer cell s. We have found that the iron chelators, deferoxamine(DFO) exert potent time- and dose-dependent inhibitory effec ts on the growth of IHOK and HN4 cells. The major mechanism of growth inhibition after DFO t reatment was by induction of apoptosis, which is supported by AnnexinV-FITC staining. cell cycle analysi s‘ DNA laddering and Hochest staining. We reported that the ch elator st rongly activates p38 MAP kinase and ex tracellul ar signal - regul ated kinase(ERK) , but not activates c-Jun N-terminal kinase/stress-activated protein kin ase(JNK/8APK) . Interl eukin -8(IL-8) is an important cytokine involved in tumor growth and angiogenesis in a va ri ety of rnalignancies‘ bu t the regulation of IL-8 in oral can cer cells are understood. We investigated whether mi togen-activatecl protein kinases pathway is involved in iron chelator-mediated IL-8 proclllction in immorta li zecl a ncl ma lignant ora l keratinocytes. In this study we examined the role of p38 ancl extracellular s ignal- reglll atecl kinase-l/2 in t he expression of IL-8 by DFO.