Department of Marine Life Science, Jeju National University, Republic of Korea.
Cancer Lett. 2010 Feb 28;288(2):204-13. doi: 10.1016/j.canlet.2009.07.002. Epub 2009 Jul 29.
We investigated the molecular effects of 3,4,2',4'-tetrahydroxychalcone (butein) treatment in two human hepatoma cancer cell lines-HepG2 and Hep3B. Butein treatment inhibited cancer cell growth by inducing G(2)/M phase arrest and apoptosis. Butein-induced G(2)/M phase arrest was associated with increased ATM, Chk1, and Chk2 phosphorylations and reduced cdc25C levels. Additionally, butein treatment enhanced inactivated phospho-Cdc2 levels, reduced Cdc2 kinase activity, and generated reactive oxygen species (ROS) that was accompanied by JNK activation. The extent of butein-induced G(2)/M phase arrest significantly decreased following pretreatment with N-acetyl-l-cysteine or glutathione and following JNK phosphorylation reduction by SP600125. Both N-acetyl-l-cysteine and glutathione also decreased butein-mediated apoptosis. Taken together, these results imply a critical role of ROS and JNK in the anticancer effects of butein.
我们研究了 3,4,2',4'-四羟基查耳酮（白杨素）处理两种人肝癌癌细胞系 HepG2 和 Hep3B 中的分子效应。白杨素通过诱导 G2/M 期阻滞和细胞凋亡抑制癌细胞生长。白杨素诱导的 G2/M 期阻滞与 ATM、Chk1 和 Chk2 磷酸化增加以及 cdc25C 水平降低有关。此外，白杨素处理增强了失活的磷酸化 Cdc2 水平，降低了 Cdc2 激酶活性，并产生了活性氧物种（ROS），同时伴随着 JNK 的激活。经 N-乙酰-L-半胱氨酸或谷胱甘肽预处理和 SP600125 降低 JNK 磷酸化后，白杨素诱导的 G2/M 期阻滞显著减少。N-乙酰-L-半胱氨酸和谷胱甘肽也降低了白杨素介导的细胞凋亡。综上所述，这些结果表明 ROS 和 JNK 在白杨素的抗癌作用中起着关键作用。
