Affiliations: CRC Beatson Laboratories, The Beatson Institute for
Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow, G61 1BD,
UK
Note: [] CRC Beatson Laboratories, The Beatson Institute for Cancer
Research, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK. Fax: +44 141
942 6521; E-mail: p.r.harrison@beatson.gla.ac.uk
Abstract: Accumulated evidence from prospective studies, intervention trials
and studies on animal models of cancer have suggested a strong inverse
correlation between selenium intake and cancer incidence. Several putative
mechanisms have been suggested to mediate the chemopreventive activities of
selenium: of these, the inhibition of cellular proliferation and the induction
of apoptosis are particularly attractive. The mitogen activated protein kinase (MAPK) pathways are known to be
important regulators of cell death and our recent work has focused on the
involvement of these pathways in selenium-induced apoptosis in primary cultures
of oral cancers and corresponding normal mucosa derived from biopsy
material. Using this system, the oral carcinoma cells were found to have
enhanced sensitivity to apoptosis when treated with certain selenium compounds
compared to normal oral mucosa. Induction of Fas ligand was associated with
selenium-induced apoptosis. Signal transduction studies suggests that selenium induces several
changes in the MAPK signalling pathways but functional intervention/inhibitor
studies indicate that activation of the JNK pathway seems to be most
important.
