Genistein Inhibits Cell Growth by Modulating Various Mitogen-Activated Protein Kinases and AKT in Cervical Cancer Cells

• Published in: Annals of the New York Academy of Sciences 2009-08, Vol.1171 (1), p.495-500
• Main Authors: Kim, Su-Hyeon, Kim, Su-Hyeong, Kim, Yong-Beom, Jeon, Yong-Tark, Lee, Sang-Chul, Song, Yong-Sang
• Format: Article
• Language: English
• Subjects: AKT; Androstadienes - pharmacology; Anthracenes - pharmacology; Anticarcinogenic Agents - pharmacology; Blotting, Western; Cancer; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Dose-Response Relationship, Drug; Enzyme Inhibitors - pharmacology; ERK1/2; Female; Flavonoids - pharmacology; genistein; Genistein - pharmacology; HeLa Cells; Humans; Imidazoles - pharmacology; Inhibition; Isoflavones; JNK; JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors; JNK Mitogen-Activated Protein Kinases - metabolism; Kinases; Mitogen-Activated Protein Kinase 1 - antagonists & inhibitors; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - antagonists & inhibitors; Mitogen-Activated Protein Kinase 3 - metabolism; Mitogen-Activated Protein Kinases - antagonists & inhibitors; Mitogen-Activated Protein Kinases - metabolism; p38 MAPK; p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors; p38 Mitogen-Activated Protein Kinases - metabolism; Phosphorylation; Phosphorylation - drug effects; Proteins; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - metabolism; Pyridines - pharmacology; Tumors; Uterine Cervical Neoplasms - metabolism; Uterine Cervical Neoplasms - pathology
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1111/j.1749-6632.2009.04899.x

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 μmol/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.