Nguyen-Khuong Terry, White Melanie Y, Hung Tzong-Tyng, Seeto Shona, Thomas Melissa L, Fitzgerald Anna M, Martucci Carlos E, Luk Sharon, Pang Shiu-Fu, Russell Pamela J, Walsh Bradley J
Minomic Pty Ltd, Frenchs Forest, New South Wales, Australia.
Proteomics. 2009 Apr;9(7):1883-92. doi: 10.1002/pmic.200700839.
Bladder cancer (BLCa) is a severe urological cancer of both men and women that commonly recurs and once invasive, is difficult to treat. MINA-05 (CK Life Sciences Int'l, Hong Kong) is a derivative of complex botanical extracts, shown to reduce cellular proliferation of bladder and prostate carcinomas. We tested the effects of MINA-05 against human BLCa cell sublines, B8, B8-RSP-GCK, B8-RSP-LN and C3, from a transitional cell carcinoma, grade IV, to determine the molecular targets of treatment by observing the cellular protein profile. Cells were acclimatised for 48 h then treated for 72 h with concentrations of MINA-05 reflecting 1/2 IC(50), IC(50) and 2 x IC(50) (n = 3) or with vehicle, (0.5% DMSO). Dose-dependant changes in protein abundance were detected and characterised using 2-dimensional electrophoresis and MS. We identified 10 proteins that underwent changes in abundance, pI and/or molecular mass in response to treatment. MINA-05 was shown to influence proteins across numerous functional classes including cytoskeletal proteins, energy metabolism proteins, protein degradation proteins and tumour suppressors, suggesting a global impact on these cell lines. This study implies that the ability of MINA-05 to retard cellular proliferation is attributed to its ability to alter cell cycling, metabolism, protein degradation and the cancer cell environment.
膀胱癌(BLCa)是一种严重的男女泌尿系统癌症,通常会复发,一旦发生侵袭则难以治疗。MINA-05(香港CK生命科学国际公司)是一种复合植物提取物的衍生物,已显示出可减少膀胱癌和前列腺癌细胞的增殖。我们测试了MINA-05对人膀胱癌细胞亚系B8、B8-RSP-GCK、B8-RSP-LN和C3(来自IV级移行细胞癌)的作用,通过观察细胞蛋白质谱来确定治疗的分子靶点。细胞适应48小时后,用反映1/2半数抑制浓度(IC(50))、IC(50)和2倍IC(50)的MINA-05浓度处理72小时(n = 3),或用溶剂(0.5%二甲亚砜)处理。使用二维电泳和质谱检测并表征蛋白质丰度的剂量依赖性变化。我们鉴定出10种蛋白质,其丰度、等电点和/或分子量因处理而发生变化。结果表明,MINA-05会影响众多功能类别的蛋白质,包括细胞骨架蛋白、能量代谢蛋白、蛋白质降解蛋白和肿瘤抑制因子,这表明其对这些细胞系具有全面影响。这项研究表明,MINA-05抑制细胞增殖的能力归因于其改变细胞周期、代谢、蛋白质降解和癌细胞环境的能力。