In vivo modulation of signaling factors involved in cell survival.

In vivo expression of cell survival factors protein kinase C (PKC), nuclear factor kappaB (NFkappaB), and extracellular signal-regulated kinase (Erk), which may contribute to the development of radioresistance following radiotherapy, was looked for. Their modulation with natural compounds (curcumin, rutin or nicotinamide) was attempted in mice bearing a serially transplanted fibrosarcoma. Expression of protein kinase C was isoform specific. No translocation of any of the isozymes was noticed following gamma-irradiation as has been reported elsewhere. None of the isoforms could be significantly inhibited by the modulators. However, significant inhibition of radiation-induced ERK and NFkappaB was observed with both curcumin and nicotinamide. Therefore we conclude that use of inhibitors of MAP kinases or NFkappaB may be a more promising strategy to enhance tumour cell killing or to prevent the development of radioresistance during radiotherapy.