Inhibition of MMP-3 activity and invasion of the MDA-MB-231 human invasive breast carcinoma cell line by bioflavonoids
Inhibition of MMP-3 activity and invasion of the MDA-MB-231 human invasive breast carcinoma cell line by bioflavonoids
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DOI：
10.1038/aps.2009.107
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发表时间：
2009-08-01
影响因子：
8.2
通讯作者：
Limtrakul, Pornngarm
中科院分区：
文献类型：
--
作者：
Phromnoi, Kanokkarn;Yodkeeree, Supachai;Limtrakul, Pornngarm
目的：基质金属蛋白酶-3是一种与肿瘤侵袭转移密切相关的酶。在这项研究中，研究了从蔬菜和水果中提取的黄酮类化合物，如栎素、山奈酚、染料木素、染料木素和大豆苷元对乳腺癌细胞株MDA-MB-231分泌和活性基质金属蛋白酶-3的调节作用。此外，我们还观察了黄酮类化合物对MDA-MB-231细胞体外侵袭的影响。方法：采用四甲基偶氮唑盐比色法确定黄酮类化合物的毒性浓度范围。用改良的Boyden小室系统评价MDA-MB-231细胞的侵袭能力。酪蛋白酶谱测定基质金属蛋白酶-3的活性。用Western blotting、酪蛋白酶谱和ELISA法检测MMP3的分泌。结果：槲皮素和山奈酚(黄酮醇)对MDAMB-231细胞的体外侵袭有明显的抑制作用，且呈浓度依赖关系，IC50值分别为27和30mU·mol/L。槲皮素和山奈酚对MMP3活性的抑制作用呈剂量依赖关系，IC50值分别为30mU/L和45mU/L。结论：与金雀异黄素、染料木素和大豆苷元相比，黄酮醇类化合物具有更强的抗侵袭能力和更强的抑制MMP3活性。相反，黄酮醇和异黄酮类化合物对基质金属蛋白酶-3的分泌均无影响。
Aim: Stromelysin 1 (matrix metalloproteinase 3; MMP-3) is an enzyme known to be involved in tumor invasion and metastasis. In this study, flavonoids from vegetables and fruits, such as quercetin, kaempferol, genistein, genistin, and daidzein, were tested for their ability to modulate the secretion and activity of MMP-3 in the MDA-MB-231 breast cancer cell line. In addition, we investigated the in vitro effects of flavonoids on MDA-MB-231 cell invasion.Methods: The toxic concentration range of flavonoids was evaluated using the MTT assay. The ability of MDA-MB-231 cells to invade was evaluated using a modified Boyden chamber system. The activity of MMP-3 was determined by casein zymography. The secretion of MMP-3 was evaluated using Western blotting, casein zymography and confirmed by ELISA.Results: Some putative flavonoids, ie, quercetin and kaempferol (flavonols), significantly inhibited the in vitro invasion of MDA-MB-231 cells in a concentration-dependent manner, with IC50 values of 27 and 30 mu mol/L, respectively. Quercetin and kaempferol also reduced MMP-3 activity in a dose-dependent manner, with IC50 values in the range of 30 mu mol/L and 45 mu mol/L, respectively. None of the flavonoids had a significant effect on the secretion of MMP-3.Conclusion: These data show that the flavonols quercetin and kaempferol have higher anti-invasion potency and higher MMP-3 inhibitory activity than isoflavones genistein, genistin and daidzein. In contrast, neither flavonols nor isoflavones have any effect on MMP-3 secretion.