尽管已知Brassinin具有抗血管生成作用,抗炎,和在结肠中的抗肿瘤作用,前列腺,乳房,肺,和肝癌,到目前为止,尚未完全了解Brassinin的潜在抗肿瘤机制。因此,在目前的研究中,探讨了Brassinin在前列腺癌中的凋亡机制。在这里,Brassinin显著增加细胞毒性并降低前-聚ADP核糖聚合酶(PARP)的表达,与DU145和LNCaP细胞相比,PC-3细胞中的pro-caspase3和B细胞淋巴瘤2(Bcl-2)。始终如一,油菜素减少了菌落的数量,并增加了PC-3细胞中的亚G1群体和末端脱氧核苷酸转移酶(TdT)dUTP尼克末端标记(TUNEL)阳性细胞。值得注意的是,油菜素抑制丙酮酸激酶M2(PKM2)的表达,葡萄糖转运蛋白1(GLUT1),己糖激酶2(HK2),和乳酸脱氢酶(LDH)作为PC-3细胞中的糖酵解蛋白。此外,油菜素显著降低SIRT1、c-Myc、和PC-3细胞中的β-catenin,也破坏了SIRT1与β-catenin的结合,在SIRT1和β-catenin之间观察到蛋白质-蛋白质相互作用(PPI)评分为0.879,spearman相关系数为0.47。值得注意的是,Brassinin显着增加PC-3细胞中活性氧(ROS)的产生。相反,ROS清除剂NAC逆转了油菜素减弱pro-PARP的能力,PC-3细胞中的pro-Caspase3、SIRT1和β-catenin。一起来看,这些发现支持Brassinin通过ROS介导的SIRT1,c-Myc,β-连环蛋白,和糖酵解蛋白作为有效的抗癌候选物。
Though
Brassinin is known to have antiangiogenic, anti-inflammatory, and antitumor effects in colon, prostate, breast, lung, and liver cancers, the underlying antitumor mechanism of
Brassinin is not fully understood so far. Hence, in the current study, the apoptotic mechanism of
Brassinin was explored in prostate cancer. Herein, Brassinin significantly increased the cytotoxicity and reduced the expressions of pro-Poly ADP-ribose polymerase (PARP), pro-caspase 3, and B-cell lymphoma 2 (Bcl-2) in PC-3 cells compared to DU145 and LNCaP cells. Consistently,
Brassinin reduced the number of colonies and increased the sub-G1 population and terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL)-positive cells in the PC-3 cells. Of note, Brassinin suppressed the expressions of pyruvate kinase-M2 (PKM2), glucose transporter 1 (GLUT1), hexokinase 2 (HK2), and lactate dehydrogenase (LDH) as glycolytic proteins in the PC-3 cells. Furthermore,
Brassinin significantly reduced the expressions of SIRT1, c-Myc, and β-catenin in the PC-3 cells and also disrupted the binding of SIRT1 with β-catenin, along with a protein-protein interaction (PPI) score of 0.879 and spearman\'s correlation coefficient of 0.47 being observed between SIRT1 and β-catenin. Of note, Brassinin significantly increased the reactive oxygen species (ROS) generation in the PC-3 cells. Conversely, ROS scavenger NAC reversed the ability of Brassinin to attenuate pro-PARP, pro-Caspase3, SIRT1, and β-catenin in the PC-3 cells. Taken together, these findings support evidence that Brassinin induces apoptosis via the ROS-mediated inhibition of SIRT1, c-Myc, β-catenin, and glycolysis proteins as a potent anticancer candidate.