Department of Foods and Nutrition, Kookmin University, Sungbuk-Gu, Seoul 136-702, South Korea.
Nutr Res. 2010 Jun;30(6):403-9. doi: 10.1016/j.nutres.2010.06.009.
alpha-Lipoic acid (LA), a naturally occurring molecule in animal and plant cells, is a potent antioxidant that reportedly exerts beneficial effects on cell proliferation and apoptosis in various cancer cell lines. However, the molecular mechanisms behind the antimetastatic property of LA are not well understood. The present study investigates the effect of LA on metastasis in a cell system. Our hypothesis is that LA inhibits metastasis via inhibition of matrix metalloproteinase (MMP) in vitro. MDA-MB-231 cells, a human breast cancer cell line, were treated with various concentrations of LA (0, 250, 500, or 1000 mumol/L) to measure metastasis, MMP activity, and mRNA expression. The viability of cells was examined by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. The effect of LA on metastasis was evaluated using the motility, migration, and invasion assay in vitro. The activity and mRNA expression of MMP-2 and MMP-9 were measured. After LA treatment, cell motility and cell migration were significantly decreased (P < .05). alpha-Lipoic acid also reduced cell invasion through a Matrigel-coated chamber (P < .05). Activities of MMP-2 and MMP-9 were decreased by LA treatment in a dose-dependent manner. RT-PCR analysis confirmed the reduction in mRNA expression level of MMP-2 and MMP-9 by LA treatment. We conclude that in this cell culture model, LA treatment inhibits cancer metastasis, and this inhibition is likely due to the decrease in the activity and mRNA expression levels of MMP-2 and MMP-9 caused by LA.
α-硫辛酸（LA）是一种存在于动植物细胞中的天然分子，是一种有效的抗氧化剂，据报道对各种癌细胞系的细胞增殖和细胞凋亡有有益的影响。然而，LA 发挥抗转移作用的分子机制尚不清楚。本研究调查了 LA 对细胞系统中转移的影响。我们的假设是，LA 通过抑制细胞外基质金属蛋白酶（MMP）来抑制转移。用不同浓度的 LA（0、250、500 或 1000 mumol/L）处理 MDA-MB-231 细胞（一种人乳腺癌细胞系）以测量转移、MMP 活性和 mRNA 表达。通过 3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四氮唑溴盐测定法检查细胞活力。通过体外运动、迁移和侵袭测定评估 LA 对转移的影响。测量 MMP-2 和 MMP-9 的活性和 mRNA 表达。LA 处理后，细胞运动和细胞迁移明显减少（P <.05）。α-硫辛酸还通过 Matrigel 包被的室减少细胞侵袭（P <.05）。LA 处理以剂量依赖性方式降低 MMP-2 和 MMP-9 的活性。RT-PCR 分析证实 LA 处理降低了 MMP-2 和 MMP-9 的 mRNA 表达水平。我们得出结论，在这种细胞培养模型中，LA 处理抑制了癌症转移，这种抑制可能是由于 LA 降低了 MMP-2 和 MMP-9 的活性和 mRNA 表达水平所致。
