Citalingam Kamini, Abas Faridah, Lajis Nordin H, Othman Iekhsan, Naidu Rakesh
Jeffery Cheah School of Medicine & Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, 47500 Bandar Sunway, Selangor, Malaysia.
Laboratory of Natural Products, Faculty of Science, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.
Molecules. 2015 Feb 17;20(2):3406-30. doi: 10.3390/molecules20023406.
Curcumin has poor in vivo absorption and bioavailability, highlighting a need for new curcumin analogues with better characteristics in these aspects. The aim of this study is to determine the anti-cancer properties of four selected curcumin analogues, on the cytotoxicity, proliferative and apoptotic effects on androgen-independent human prostate cancer cells (PC-3 and DU 145). Initial cytotoxicity screening showed MS17 has the highest cell inhibitory effect, with EC50 values of 4.4 ± 0.3 and 4.1 ± 0.8 µM, followed by MS13 (7.5 ± 0.1 and 7.4 ± 2.6 µM), MS49 (14.5 ± 1.2 and 12.3 ± 2.3 µM) and MS40E (28.0 ± 7.8 and 30.3 ± 1.9 µM) for PC-3 and DU 145 cells, respectively. Time-dependent analysis also revealed that MS13 and MS17 displayed a greater anti-proliferative effect than the other compounds. MS17 was chosen based on the high selectivity index value for further analysis on the morphological and biochemical hallmarks of apoptosis. Fluorescence microscopy analysis revealed apoptotic changes in both treated prostate cancer cells. Relative caspase-3 activity increased significantly at 48 h in PC-3 and 12 h in DU 145 cells. Highest enrichment of free nucleosomes was noted at 48 h after treatment with MS17. In conclusion, MS17 demonstrated anti-proliferative effect and induces apoptosis in a time and dose-dependent manner suggesting its potential for development as an anti-cancer agent for androgen-independent prostate cancer.
姜黄素在体内的吸收和生物利用度较差，这凸显了对具有更好这些方面特性的新型姜黄素类似物的需求。本研究的目的是确定四种选定的姜黄素类似物对雄激素非依赖性人前列腺癌细胞（PC-3和DU 145）的细胞毒性、增殖和凋亡作用的抗癌特性。初步细胞毒性筛选显示，MS17具有最高的细胞抑制作用，PC-3细胞和DU 145细胞的半数有效浓度（EC50）值分别为4.4±0.3和4.1±0.8 μM，其次是MS13（7.5±0.1和7.4±2.6 μM）、MS49（14.5±1.2和12.3±2.3 μM）和MS40E（28.0±7.8和30.3±1.9 μM）。时间依赖性分析还表明，MS13和MS17比其他化合物表现出更大的抗增殖作用。基于高选择性指数值选择MS17进行凋亡的形态学和生化特征的进一步分析。荧光显微镜分析显示，两种处理后的前列腺癌细胞均有凋亡变化。PC-3细胞在48小时时和DU 145细胞在12小时时，半胱天冬酶-3相对活性显著增加。用MS17处理48小时后，游离核小体的富集程度最高。总之，MS17表现出抗增殖作用，并以时间和剂量依赖性方式诱导凋亡，表明其有潜力开发成为雄激素非依赖性前列腺癌的抗癌药物。
