Genistein inhibits cell growth by modulating various mitogen-activated protein kinases and AKT in cervical cancer cells.
Genistein, a soy-derived isoflavone, inhibits growth of tumor cells from various malignancies. Here we investigated the effect of genistein on the growth of cervical cancer cells (HeLa and CaSki) and its possible mechanism. Genistein significantly suppressed cell growth of HeLa and CaSki cells at concentrations of 20 and 60 micromol/L, respectively, for 24 h. Western blotting analysis showed that genistein reduced phosphorylation of AKT and extracellular signal-regulated kinase (ERK)-1/2 and induced phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK). Moreover, inhibition of ERK1/2 activity enhanced cell growth inhibition by genistein, whereas inhibition of p38 MAPK activity rescued from genistein-mediated growth inhibition. Interestingly, inhibition of AKT activity recovered genistein-induced growth inhibition in CaSki cells but did not in HeLa cells. However, inhibition of JNK activity seemed to have little effect on cell growth inhibition by genistein. Taken together, these results suggest that genistein could inhibit cell growth by inhibiting ERK1/2 activity and activating p38 MAPK.
Kim
Su-Hyeon
SH
Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Kim
Su-Hyeong
SH
Kim
Yong-Beom
YB
Jeon
Yong-Tark
YT
Lee
Sang-Chul
SC
Song
Yong-Sang
YS
D000730:Androstadienes / Q000494:pharmacology; D000873:Anthracenes / Q000494:pharmacology; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology; D000077191:Wortmannin; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D000730:Androstadienes; D000873:Anthracenes; D016588:Anticarcinogenic Agents; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D011725:Pyridines; C432165:pyrazolanthrone; D019833:Genistein; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D000077191:Wortmannin