Fu Yue, Hsieh Tze-chen, Guo Junqiao, Kunicki Jan, Lee Marietta Y W T, Darzynkiewicz Zbigniew, Wu Joseph M
Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA.
Biochem Biophys Res Commun. 2004 Sep 10;322(1):263-70. doi: 10.1016/j.bbrc.2004.07.094.
Licochalcone (LA) is a novel estrogenic flavonoid isolated from PC-SPES composition herb licorice root that was reported to show significant antitumor activity in various malignant human cell lines. To better understand its anti-CaP activities, we have investigated LA-elicited growth control and induction of apoptosis using androgen-independent p53-null PC-3 prostate cancer cells. LA induced modest level of apoptosis but had more pronounced effect on cell cycle progression arresting cells in G2/M, accompanied by suppression of cyclin B1 and cdc2. It also inhibited phosphorylation of Rb, specifically phosphorylation of S780 with no change of phosphorylation status of T821, decreased expression of transcription factor E2F concurrent with reduction of cyclin D1, down-regulation of CDKs 4 and 6, but increased cyclin E expression. These findings provide mechanistic explanation for LA activity and suggest that it may be considered as a chemopreventive agent and its anticancer properties should be further explored.
甘草查尔酮（LA）是一种从PC-SPES复方草药甘草根中分离出的新型雌激素类黄酮，据报道其在多种人类恶性细胞系中显示出显著的抗肿瘤活性。为了更好地了解其抗前列腺癌（CaP）活性，我们使用雄激素非依赖性、p53基因缺失的PC-3前列腺癌细胞研究了LA诱导的生长控制和细胞凋亡。LA诱导了适度水平的细胞凋亡，但对细胞周期进程有更显著的影响，使细胞停滞在G2/M期，同时伴随着细胞周期蛋白B1和细胞周期蛋白依赖性激酶2（cdc2）的抑制。它还抑制视网膜母细胞瘤（Rb）的磷酸化，特别是S780位点的磷酸化，而T821位点的磷酸化状态没有变化，同时降低转录因子E2F的表达并伴随细胞周期蛋白D1的减少，下调细胞周期蛋白依赖性激酶4（CDK4）和细胞周期蛋白依赖性激酶6（CDK6），但增加细胞周期蛋白E的表达。这些发现为LA的活性提供了机制解释，并表明它可能被视为一种化学预防剂，其抗癌特性应进一步探索。
