Department of Medical Analysis, School of Pharmaceutical Sciences, Zhengzhou University, Ke Xue Road, Zhengzhou, China; Henan Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou University, Ke Xue Road, Zhengzhou, China.
Department of Pharmaceutics, School of Pharmaceutical Sciences, Zhengzhou University, Ke Xue Road, Zhengzhou, China.
J Pharm Biomed Anal. 2020 Jul 15;186:113288. doi: 10.1016/j.jpba.2020.113288. Epub 2020 Apr 4.
Flavokawain A (FKA), a major chalcone in kava extracts, has exhibited anti-proliferative and apoptotic effects in the prostate cancer. However, the molecular mechanism of FKA remains unclear. In this study, FKA induces cell apoptosis and cell cycle arrest in a G2M phase to prostate cancer cells. FKA interferes with tubulin polymerization and inhibits survivin expression in PC3 cells. Molecular docking simulation experiment finds that FKA can bind to colchicine binding sites that inhibit tubulin polymerization. FKA treatment regulates the glutamine metabolism pathway in PC3 cells by reducing intracellular glutamine, glutamic and proline. FKA treatment also decreases the GSH content by decreasing the activity of GSH synthetase (GSS) and increasing the activity of glutathione thiol transferase (GSTP1), which subsequently induces ROS production and PC3 cell apoptosis.
卡瓦胡椒素 A（FKA）是卡瓦提取物中的一种主要查尔酮，已显示出对前列腺癌的抗增殖和促凋亡作用。然而，FKA 的分子机制尚不清楚。在这项研究中，FKA 诱导前列腺癌细胞凋亡和 G2M 期细胞周期停滞。FKA 干扰微管聚合并抑制 PC3 细胞中存活素的表达。分子对接模拟实验发现，FKA 可以与抑制微管聚合的秋水仙碱结合位点结合。FKA 处理通过减少细胞内谷氨酰胺、谷氨酸和脯氨酸来调节 PC3 细胞中的谷氨酰胺代谢途径。FKA 处理还通过降低谷胱甘肽合成酶（GSS）的活性和增加谷胱甘肽硫转移酶（GSTP1）的活性来降低 GSH 含量，从而随后诱导 ROS 产生和 PC3 细胞凋亡。
