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.
Kumar Mitra
Anirban
A
Radiation Biology and Health Sciences Division Bhabha Atomic Research Centre Trombay, Mumbai, India.
Krishna
Malini
M
D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival; D003474:Curcumin / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000096:biosynthesis; D048052:Mitogen-Activated Protein Kinase 3 / Q000096:biosynthesis; D016328:NF-kappa B / Q000096:biosynthesis* / Q000378:metabolism; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000532:radiotherapy*; D009536:Niacinamide / Q000494:pharmacology; D020033:Protein Isoforms; D011493:Protein Kinase C / Q000096:biosynthesis* / Q000737:chemistry; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha; D051745:Protein Kinase C-delta; D021381:Protein Transport; D012431:Rutin / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction; D000099221:Protein Kinase C zeta
D003474:Curcumin; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D016328:NF-kappa B; D009536:Niacinamide; D020033:Protein Isoforms; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha; D051745:Protein Kinase C-delta; D012431:Rutin; D000099221:Protein Kinase C zeta; C497259:Prkcd protein, mouse; C496630:Prkca protein, mouse