Vijayababu Marati R, Arunkumar A, Kanagaraj P, Arunakaran J
Department of Endocrinology, Dr. ALM Postgraduate Institute of Basic Medical Sciences, University of Madras, Taramani campus, Chennai-600 113, INDIA.
J Carcinog. 2006 Apr 6;5:10. doi: 10.1186/1477-3163-5-10.
Quercetin, the predominant flavonoid, has been reported to lower the risk of several cancers. This flavonoid found in onion, grapes, green vegetables, etc. has been shown to possess potent antiproliferative effects against various malignant cells. This study was designed to investigate its effects on insulin-like growth factors (IGFs) and their binding protein-3 (IGFBP-3) proteins secretion and also apoptosis induction in the human prostate cancer cell line, PC-3.
We evaluated the secretion of IGF-I, -II and IGFBP-3 in quercetin treated cells by immunoradiometric (IRMA) method. Apoptosis was studied in quercetin treated cells by TUNEL and DNA fragmentation. Protein expressions of Bcl-2, Bcl-xL, Bax and caspase-3 were studied by western blot.
At a dose of 100 microM concentration, we observed increased IGFBP-3 accumulation in PC-3 cells conditioned medium with a dose dependent increase with 2 fold over a base line, and significantly reduced the both IGF-I and IGF-II levels. Apoptosis induction was also confirmed by TUNEL assay. Bcl-2 and Bcl-xL protein expressions were significantly decreased and Bax and caspase-3 were increased.
These results suggest that the decreased level of IGFs could be due to the increased levels of IGFBP-3, because of the high binding affinity towards IGFs, thereby decreasing the cell proliferation. The increased level of IGFBP-3 was associated with increased pro-apoptotic proteins and apoptosis in response to quercetin, suggesting it may be a p53-independent effector of apoptosis in prostate cancer cells.
槲皮素是主要的类黄酮，据报道可降低多种癌症的风险。这种存在于洋葱、葡萄、绿色蔬菜等中的类黄酮已被证明对各种恶性细胞具有强大的抗增殖作用。本研究旨在调查其对胰岛素样生长因子（IGFs）及其结合蛋白-3（IGFBP-3）蛋白分泌的影响，以及对人前列腺癌细胞系PC-3凋亡的诱导作用。
我们通过免疫放射分析（IRMA）方法评估槲皮素处理细胞中IGF-I、-II和IGFBP-3的分泌。通过TUNEL和DNA片段化研究槲皮素处理细胞中的凋亡。通过蛋白质印迹法研究Bcl-2、Bcl-xL、Bax和caspase-3的蛋白表达。
在100微摩尔浓度下，我们观察到PC-3细胞条件培养基中IGFBP-3积累增加，呈剂量依赖性增加，比基线增加2倍，并显著降低了IGF-I和IGF-II水平。TUNEL分析也证实了凋亡诱导。Bcl-2和Bcl-xL蛋白表达显著降低，Bax和caspase-3表达增加。
这些结果表明，IGFs水平降低可能是由于IGFBP-3水平升高，因为其对IGFs具有高结合亲和力，从而降低细胞增殖。IGFBP-3水平升高与槲皮素诱导的促凋亡蛋白增加和凋亡相关，表明它可能是前列腺癌细胞中一种不依赖p53的凋亡效应物。
