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• W2884458804 abstract "4838 Our previous studies have shown that PBN, a prototypical nitrone, has anti-cancer activity in the development of choline deficiency (CD)-induced hepatocellular carcinoma in a rat model by shifting the equilibrium from neoplasia to apoptosis and the inhibition of nitric oxide (NO) formation may be involved in its anti-cancer activity. Although a variety of approaches have attempted to reveal the mechanisms of PBN inhibition of tumor development, the exact mechanism remains elusive. In present results, we explored the effect of PBN on the combined cytokines (INF-γ, TNF-α and IL-1β)-induced apoptosis, particularly on the expression of iNOS and HIF-1α in liver tumor cell lines, Hepa 1-6 and Hepa 1C1C7. First we tested the ability of hypoxia at various oxygen concentrations as well as anoxia to induce HIF-1α expression in the cell lines and the possible effects of the combined cytokines, on the expression of iNOS and HIF-1α. The results demonstrated that there were dramatic increases in the expression of HIF-1α when the cells were exposed to anoxia and in the expression of iNOS when the cells were exposed to the combined cytokines (ITI). A significant increase in NO production measured as nitrite in the media was also observed. The most important findings were that when PBN was added in culture media, the anoxia-induced expression of HIF-1α and ITI-induced iNOS were inhibited. Additionally, a reduction of ITI-induced NO in the media was observed when the cells exposed to PBN. Furthermore, we tested the effect of PBN on induction of apoptosis measured as DNA fragmentation at G0/G1 phase. An enhanced increase in apoptosis was observed when the cells were exposed to ITI and PBN, particularly under anoxia. Thus, these preliminary results not only confirmed our previous observations in vivo, but also clearly indicated that regulation of iNOS and HIF-1α was involved in the PBN anti-cancer activity. The discovery that PBN inhibits HIF-1α activation suggests that nitrones represent a potential new class of anti-cancer therapeutics. This research is supported in part by NIH RO1CA82506 and OARS AR05.2-041." @default.
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• W2884458804 date "2007-05-01" @default.
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• W2884458804 title "Involvement of iNOS and HIF-1α in the anti-cancer activity of α-phenyl-N-tert-butyl nitrone (PBN) in liver tumor cells" @default.
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