RESUMO
Objective To investigate the effect of genistein on the proliferation of human lung cancer PC14 cells and the underlying mechanisms. Methods Cell proliferation was examined using the MTT and colony formation assays. Western blotting was used to analyze protein expression levels. Results Genistein significantly inhibited the proliferation of PC14 cells in a concentration and time dependent manner. PD98059, SB203580, and SP100625, three specific inhibitors of the MAPK pathway, significantly inhibited the proliferation of PC14 cells. Moreover, genistein inhibited the phosphorylation of ERK and JNK in a dose dependent manner. Conclusion Genistein can inhibit the proliferation of PC14 cells, which may be related to its inhibitory effect on ERK and JNK activation.
RESUMO
Increased expression of Transglutaminases 2 (TGase 2, TGase C) was observed in PC-14 human lung cancer cells in association with doxorubicin resistance and the reduction of the enzyme expression was correlated with the increasing cytotoxicity of the drug (Han and Park, 1999). Hydrogen peroxide was suggested to be a key mediator for doxorubicin-induced DNA fragmentation leading to apoptosis. A possible role of hydrogen peroxide as a putative mediator of TGase 2 expression in the doxorubicin sensitive PC-14 cells was examined. TGase 2 expression was increased in PC-14 cells treated with doxorubicin in a dose-dependent manner resulting in the concomitant increase of reactive oxygen species. The rise of TGase 2 expression by doxorubicin treatment was inhibited by N-acetylcysteine or glutathione treatment, while direct addition of hydrogen peroxide to PC-14 cells induced TGase 2 expression. These results suggest that generation of hydrogen peroxide induced by doxorubicin treatment is one of the key factors in an enhancement of TGase 2 expression in PC-14 cells.