Implication of mitogen-activated protein kinase in the induction of G1 cell cycle arrest and gadd45 expression by the carotenoid fucoxanthin in human cancer cells.
BACKGROUND
The precise mechanism of the anti-tumor action of fucoxanthin has yet to be elucidated. We previously reported that gadd45a and gadd45b might play a role in the G1 arrest induced by fucoxanthin. In the present study, we show that several MAPKs modulate the induction of gadd45 and G1 arrest


METHODS
HepG2 and DU145 cells were used. The cell cycle was analyzed using flow cytometry. Expression of gadd45 was assayed by Northern blot and/or quantitative RT-PCR analyses. Activation of MAPK was assayed by Western blot analysis.


RESULTS
Inhibition of p38 MAPK enhanced the induction ofgadd45a expression and G1 arrest by fucoxanthin in HepG2 cells. Inhibition of ERK enhanced gadd45b expression but had no effect on the induction of G1 arrest by fucoxanthin in HepG2 cells. Inhibition of SAPK/JNK suppressed the induction of gadd45a expression and G1 arrest by fucoxanthin in DU145 cells. These data suggest that gadd45a is closely related with the G1 arrest induced by fucoxanthin, and that the pattern of MAPK involvement in the induction of gadd45a and G1 arrest by fucoxanthin differs depending on the cell type.


CONCLUSIONS
The implication of GADD45 and MAPK involvement in the anti-tumor action of carotenoids is first described.
Satomi
Yoshiko
Y
Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. ysatomi@koto.kpu-m.ac.jp
Nishino
Hoyoku
H
D002453:Cell Cycle / Q000187:drug effects* / Q000502:physiology; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D016193:G1 Phase / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009687:Nuclear Proteins / Q000096:biosynthesis*; D024341:Xanthophylls / Q000494:pharmacology*; D000097642:GADD45 Proteins
D018797:Cell Cycle Proteins; D020928:Mitogen-Activated Protein Kinases; D009687:Nuclear Proteins; D024341:Xanthophylls; C439070:GADD45A protein, human; D000097642:GADD45 Proteins; C025164:fucoxanthin