Vijayababu M R, Arunkumar A, Kanagaraj P, Venkataraman P, Krishnamoorthy G, Arunakaran J
Department of Endocrinology, Dr. ALM Postgraduate Institute of Basic Medical Sciences, University of Madras, Taramani campus, Chennai, 600 113, India.
Mol Cell Biochem. 2006 Jul;287(1-2):109-16. doi: 10.1007/s11010-005-9085-3. Epub 2006 Apr 28.
Cancer metastasis, involving multiple processes and various cytophysiological changes, is a primary cause of cancer death and may complicate the clinical management, even lead to death. Quercetin is a flavonoid and widely used as an antioxidant and recent studies have revealed its pleiotropic anticancer and antiproliferative capabilities. Gelatinases A and B (matrixmetalloproteinases 2 and 9) are enzymes known to involve in tumor invasion and metastases. In this study, we observed the precise involvement of quercetin role on these proteinases expression and activity.
PC-3 cells were treated with quercetin at various concentrations (50 and 100 microM), for 24 h period and then subjected to western blot analysis to investigate the impact of quercetin on matrix metalloproteinase-2 (MMP-2) and 9 (MMP-9) expressions. Conditioned medium and cell lysate of quercetin-treated PC-3 cells were subjected to western blot analysis for proteins expression of MMP-2 and MMP-9. Gelatin zymography was also performed in quercetin treated PC-3 cells.
The results showed that quercetin treatment decreased the expressions of MMP-2 and MMP-9 in dose-dependent manner. The level of pro-MMP-9 was found to be high in the 100 microM quercetin-treated cell lysate of PC-3 cells, suggesting inhibitory role of quercetin on pro-MMP-9 activation. Gelatin zymography study also showed the decreased activities of MMP-2 and MMP-9 in quercetin treated cells.
Hence, we speculated that inhibition of metastasis-specific MMPs in cancer cells may be one of the targets for anticancer function of quercetin, and thus provides the molecular basis for the development of quercetin as a novel chemopreventive agent for metastatic prostate cancer.
癌症转移涉及多个过程和各种细胞生理变化,是癌症死亡的主要原因,可能使临床治疗复杂化,甚至导致死亡。槲皮素是一种黄酮类化合物,广泛用作抗氧化剂,最近的研究揭示了其多效性抗癌和抗增殖能力。明胶酶A和B(基质金属蛋白酶2和9)是已知参与肿瘤侵袭和转移的酶。在本研究中,我们观察了槲皮素对这些蛋白酶表达和活性的确切作用。
用不同浓度(50和100微摩尔)的槲皮素处理PC-3细胞24小时,然后进行蛋白质印迹分析,以研究槲皮素对基质金属蛋白酶-2(MMP-2)和9(MMP-9)表达的影响。对经槲皮素处理的PC-3细胞的条件培养基和细胞裂解物进行蛋白质印迹分析,以检测MMP-2和MMP-9的蛋白质表达。还对经槲皮素处理的PC-3细胞进行了明胶酶谱分析。
结果表明,槲皮素处理以剂量依赖性方式降低了MMP-2和MMP-9的表达。在经100微摩尔槲皮素处理的PC-3细胞裂解物中,前MMP-9水平较高,表明槲皮素对前MMP-9激活具有抑制作用。明胶酶谱研究还显示,经槲皮素处理的细胞中MMP-2和MMP-9的活性降低。
因此,我们推测抑制癌细胞中转移特异性MMPs可能是槲皮素抗癌功能的靶点之一,从而为将槲皮素开发为转移性前列腺癌的新型化学预防剂提供了分子基础。