College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.
Int J Mol Sci. 2023 Sep 10;24(18):13912. doi: 10.3390/ijms241813912.
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.
尽管 Brassinin 已被证实具有抗血管生成、抗炎和抗肿瘤作用，可用于治疗结肠癌、前列腺癌、乳腺癌、肺癌和肝癌，但迄今为止，其抗肿瘤的潜在机制尚未完全阐明。因此，在本研究中，探讨了 Brassinin 在前列腺癌中的凋亡机制。结果表明，与 DU145 和 LNCaP 细胞相比，Brassinin 显著增加了 PC-3 细胞的细胞毒性，降低了前多聚 ADP-核糖聚合酶（PARP）、前胱天蛋白酶 3 和 B 细胞淋巴瘤 2（Bcl-2）的表达。一致地，Brassinin 减少了 PC-3 细胞集落的数量，增加了亚 G1 群体和末端脱氧核苷酸转移酶（TdT）dUTP 缺口末端标记（TUNEL）阳性细胞的数量。值得注意的是，Brassinin 抑制了 PC-3 细胞中糖酵解蛋白丙酮酸激酶-M2（PKM2）、葡萄糖转运蛋白 1（GLUT1）、己糖激酶 2（HK2）和乳酸脱氢酶（LDH）的表达。此外，Brassinin 显著降低了 PC-3 细胞中 SIRT1、c-Myc 和 β-连环蛋白的表达，同时也破坏了 SIRT1 与 β-连环蛋白的结合，观察到 SIRT1 与 β-连环蛋白之间的蛋白质-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 显著增加了 PC-3 细胞中的活性氧（ROS）生成。相反，ROS 清除剂 NAC 逆转了 Brassinin 减弱 PC-3 细胞中 pro-PARP、pro-Caspase3、SIRT1 和 β-连环蛋白的能力。综上所述，这些发现支持了 Brassinin 通过 ROS 介导的抑制 SIRT1、c-Myc、β-连环蛋白和糖酵解蛋白诱导细胞凋亡的证据，作为一种潜在的抗癌候选药物。
