Department of Marine Life Sciences, Jeju National University, Jeju 63243, Republic of Korea; Department of Biological Sciences, Faculty of Applied Science, University of Rajarata, Mihintale 50300, Sri Lanka.
Department of Marine Life Sciences, Jeju National University, Jeju 63243, Republic of Korea.
Food Chem Toxicol. 2018 Feb;112:1-10. doi: 10.1016/j.fct.2017.12.028. Epub 2017 Dec 16.
Butein is a biologically active flavonoid isolated from the bark of Rhus verniciflua Stokes, which is known to have therapeutic potential against various cancers. Notably, butein inhibits cancer cell growth by inducing G/M phase arrest and apoptosis. Butein-induced G/M phase arrest is associated with increased phosphorylation of ataxia telangiectasia mutated (ATM) and Chk1/2, and consequently, with reduced cdc25C levels. In addition, butein-induced apoptosis is mediated through the activation of caspase-3, which is associated with changes in the expression of Bcl-2 and Bax proteins. Intriguingly, butein sensitizes cells to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis via ERK-mediated Sp1 activation, which promotes the transcription of specific death receptor 5. Butein also inhibits the migration and invasion of human cancer cells by suppressing nuclear factor-κB- and extracellular signal-regulated kinases 1/2-mediated expression of matrix metalloproteinase-9 and vascular endothelial growth factor. Additionally, butein downregulates the expression of human telomerase reverse transcriptase and causes a concomitant decrease in telomerase activity. These findings provide the basis for the pharmaceutical development of butein. The aim of this review is to provide an update on the mechanisms underlying the anticancer activity of butein, with a special focus on its effects on different cellular signaling cascades.
染料木黄酮是从漆树 Rhus verniciflua Stokes 的树皮中分离得到的一种具有生物活性的类黄酮，已知其具有治疗多种癌症的潜力。值得注意的是，染料木黄酮通过诱导 G/M 期阻滞和细胞凋亡来抑制癌细胞生长。染料木黄酮诱导的 G/M 期阻滞与 ataxia telangiectasia mutated (ATM) 和 Chk1/2 的磷酸化增加有关，从而导致 cdc25C 水平降低。此外，染料木黄酮诱导的细胞凋亡是通过 caspase-3 的激活介导的，这与 Bcl-2 和 Bax 蛋白表达的变化有关。有趣的是，染料木黄酮通过 ERK 介导的 Sp1 激活使细胞对肿瘤坏死因子相关凋亡诱导配体诱导的凋亡敏感，从而促进特定死亡受体 5 的转录。染料木黄酮还通过抑制核因子-κB 和细胞外信号调节激酶 1/2 介导的基质金属蛋白酶-9 和血管内皮生长因子的表达来抑制人癌细胞的迁移和侵袭。此外，染料木黄酮下调人端粒酶逆转录酶的表达，并导致端粒酶活性的相应降低。这些发现为染料木黄酮的药物开发提供了依据。本综述的目的是提供关于染料木黄酮抗癌活性的机制的最新信息，特别关注其对不同细胞信号通路的影响。
