Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China.
Phytomedicine. 2010 Nov;17(13):1000-5. doi: 10.1016/j.phymed.2010.03.018.
Tetrandrine (TET), a bis-benzylisoquinoline alkaloid isolated from the root of Hang-Fang-Chi (Stephenia tetrandra S Moore), exhibits broad pharmacological effects, including anti-tumor activity. Recently, the beneficial effects of TET on cytotoxicity towards tumor cells, radiosensitization, circumventing multidrug resistance, normal tissue radioprotection, and antiangiogenesis have been examined extensively. To explore the potential molecular mechanism of the anti-tumor effect of TET, we applied proteomic tools to profile the proteins in HepG2 cells subjected to TET treatment. The levels of 39 proteins in cells exposed to TET (IC₅₀=5±0.6 μg/ml) for 48 h were observed to undergo significant alterations. Six proteins were identified by matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) using peptide fingerprinting from 10 protein spots (density difference >1.5-fold between the control and TET-treated group). Among them, 5 proteins were downregulated (proteasome activator complex subunit 3, 40S ribosomal protein S12, phosphoglycerate mutase 1, destrin, transaldolase) and 1 protein was upregulated (guanylate kinase 1) by TET treatment in HepG2 cells as determined by spot volume (P<0.05). Most of the identified proteins were associated with tumor growth, migration, and anti-tumor drug resistance. These data will be helpful in elucidating the molecular mechanism of TET's anti-tumor effect in HepG2 cells.
汉防己甲素(TET)是从防己科千金藤属植物粉防己(Stephania tetrandra S Moore)的根中分离得到的一种双苄基异喹啉生物碱,具有广泛的药理作用,包括抗肿瘤活性。最近,TET 对肿瘤细胞的细胞毒性、放射增敏作用、克服多药耐药性、正常组织放射防护和抗血管生成的有益作用已被广泛研究。为了探讨 TET 抗肿瘤作用的潜在分子机制,我们应用蛋白质组学工具对 TET 处理的 HepG2 细胞中的蛋白质进行了分析。观察到暴露于 TET(IC₅₀=5±0.6μg/ml)48 小时的细胞中 39 种蛋白质的水平发生了显著变化。通过基质辅助激光解吸/电离飞行时间质谱(MALDI-TOF-MS)使用从 10 个蛋白质斑点(对照组和 TET 处理组之间的密度差异>1.5 倍)获得的肽指纹图谱鉴定了 6 种蛋白质。其中,在 HepG2 细胞中,TET 处理下调了 5 种蛋白质(蛋白酶体激活复合物亚单位 3、40S 核糖体蛋白 S12、磷酸甘油酸变位酶 1、destrin、转醛醇酶),上调了 1 种蛋白质(鸟苷酸激酶 1),这是通过斑点体积确定的(P<0.05)。鉴定出的大多数蛋白质与肿瘤生长、迁移和抗肿瘤药物耐药性有关。这些数据将有助于阐明 TET 在 HepG2 细胞中抗肿瘤作用的分子机制。