Kim Su-Hyeon, Kim Su-Hyeong, Kim Yong-Beom, Jeon Yong-Tark, Lee Sang-Chul, Song Yong-Sang
Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Ann N Y Acad Sci. 2009 Aug;1171:495-500. 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 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.
染料木黄酮是一种源自大豆的异黄酮，可抑制多种恶性肿瘤细胞的生长。在此，我们研究了染料木黄酮对宫颈癌细胞（HeLa和CaSki）生长的影响及其可能机制。染料木黄酮在浓度分别为20和60微摩尔/升时，作用24小时，能显著抑制HeLa和CaSki细胞的生长。蛋白质印迹分析表明，染料木黄酮可降低AKT和细胞外信号调节激酶（ERK）-1/2 的磷酸化水平，并诱导p38丝裂原活化蛋白激酶（MAPK）和c-Jun氨基末端激酶（JNK）的磷酸化。此外，抑制ERK1/2活性可增强染料木黄酮对细胞生长的抑制作用，而抑制p38 MAPK活性则可从染料木黄酮介导的生长抑制中挽救细胞。有趣的是，抑制AKT活性可恢复染料木黄酮诱导的CaSki细胞生长抑制，但对HeLa细胞无效。然而，抑制JNK活性似乎对染料木黄酮抑制细胞生长的作用影响不大。综上所述，这些结果表明染料木黄酮可通过抑制ERK1/2活性和激活p38 MAPK来抑制细胞生长。
