Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei 11031, Taiwan.
Biomed Res Int. 2013;2013:579859. doi: 10.1155/2013/579859. Epub 2013 May 8.
Ferulic acid (4-hydroxy-3-methoxycinnamic acid) (FA) is a ubiquitous health beneficial phenolic acid. Although FA has shown a diversity of biological activities including anti-inflammatory, antihypercholesterolemic and anticancer bioactivities, studies revealing its adverse effects are accumulating. Recently, 3D-cultures are shown to exhibit uniquely biological behaviors different from that of 2D cultures. To understand whether the cytotoxicity of FA against the T24 cell line (a bladder cancer cell line) in 2D-culture could consistently retain similar bioactivity if cultured in the 3D-systems, we conducted this experiment with 2 mM FA. Much higher cytotoxicity was found for 3D- than 2D-culture, showing (2D vs. 3D): apoptotic rates, 64% and 76%; cell killing rates, 3.00 × 10(5) cells mmol(-1)·h(-1) and 2.63 × 10(6) cells mmol(-1)·h(-1), attaining a 8.77-fold. FA upregulated the activities at 72 h (2D vs. 3D in folds that of control): SOD, 1.73-folds (P < 0.05) versus 3.18 folds (P < 0.001); and catalase, 2.58 versus 1.33-folds. Comparing to the control (without FA), Bcl-2 was prominently downregulated while Bax, caspase-3 and cleaved caspase-9 were more upregulated in 3D-cultures (P < 0.05). Conclusively, different microenvironments could elicit different biological significance which in part can be ascribed to different mass transport rate.
阿魏酸(4-羟基-3-甲氧基肉桂酸)(FA)是一种普遍存在的有益健康的酚酸。尽管 FA 表现出多种生物活性,包括抗炎、抗高胆固醇血症和抗癌活性,但揭示其不良反应的研究正在增加。最近,3D 培养显示出与 2D 培养不同的独特生物学行为。为了了解 FA 对 T24 细胞系(膀胱癌细胞系)的细胞毒性在 2D 培养中如果在 3D 系统中培养是否能保持相似的生物活性,我们用 2mM FA 进行了这项实验。3D 培养的细胞毒性明显高于 2D 培养,显示出(2D 与 3D 相比):凋亡率分别为 64%和 76%;细胞杀伤率分别为 3.00×10(5)细胞 mmol(-1)·h(-1)和 2.63×10(6)细胞 mmol(-1)·h(-1),达到 8.77 倍。FA 在 72 小时上调了活性(2D 与 3D 相比,是对照组的倍数):SOD,1.73 倍(P<0.05)与 3.18 倍(P<0.001);和过氧化氢酶,2.58 倍与 1.33 倍。与对照组(无 FA)相比,Bcl-2 在 3D 培养中明显下调,而 Bax、caspase-3 和 cleaved caspase-9 上调更多(P<0.05)。总之,不同的微环境可能会产生不同的生物学意义,这在一定程度上可以归因于不同的质量传输速率。