Lunasin 诱导人转移性结肠癌细胞凋亡，并改变细胞外基质和细胞黏附相关基因的表达。

Lunasin induces apoptosis and modifies the expression of genes associated with extracellular matrix and cell adhesion in human metastatic colon cancer cells.

机构信息

Department of Food Science and Human Nutrition, University of Illinois, Urbana-Champaign, IL 61801, USA.

出版信息

Mol Nutr Food Res. 2011 Apr;55(4):623-34. doi: 10.1002/mnfr.201000419. Epub 2011 Jan 5.

DOI:10.1002/mnfr.201000419

PMID:21462330

Abstract

SCOPE

Lunasin is an arginine-glycine-aspartic acid (RGD) cancer preventive peptide. The objective was to evaluate the potential of lunasin to induce apoptosis in human colon cancer cells and their oxaliplatin-resistant (OxR) variants, and its effect on the expression of human extracellular matrix and adhesion genes.

METHODS AND RESULTS

Various human colon cancer cell lines which underwent metastasis were evaluated in vitro using cell flow cytometry and fluorescence microscopy. Lunasin cytotoxicity to different colon cancer cells correlated with the expression of α(5) b(1) integrin, being most potent to KM12L4 cells (IC(50) = 13 μM). Lunasin arrested cell cycle at G2/M phase with concomitant increase in the expression of cyclin-dependent kinase inhibitors p21 and p27. Lunasin (5-25 μM) activated the apoptotic mitochondrial pathway as evidenced by changes in the expressions of Bcl-2, Bax, nuclear clusterin, cytochrome c and caspase-3 in KM12L4 and KM12L4-OxR. Lunasin increased the activity of initiator caspase-9 leading to the activation of caspase-3 and also modified the expression of human extracellular matrix and adhesion genes, downregulating integrin α(5), SELE, MMP10, integrin β(2) and COL6A1 by 5.01-, 6.53-, 7.71-, 8.19- and 10.10-fold, respectively, while upregulating COL12A1 by 11.61-fold.

CONCLUSION

Lunasin can be used in cases where resistance to chemotherapy developed.

摘要

范围

Lunasin 是一种精氨酸-甘氨酸-天冬氨酸（RGD）癌症预防肽。目的是评估 lunasin 诱导人结肠癌细胞及其奥沙利铂耐药（OxR）变体凋亡的潜力，及其对人细胞外基质和黏附基因表达的影响。

方法和结果

使用细胞流式细胞术和荧光显微镜，在体外评估了各种发生转移的人结肠癌细胞系。Lunasin 对不同结肠癌细胞的细胞毒性与 α(5) b(1) 整联蛋白的表达相关，对 KM12L4 细胞最为有效（IC(50) = 13 μM）。Lunasin 将细胞周期阻滞在 G2/M 期，同时 cyclin 依赖性激酶抑制剂 p21 和 p27 的表达增加。Lunasin（5-25 μM）通过改变 KM12L4 和 KM12L4-OxR 中 Bcl-2、Bax、核聚集素、细胞色素 c 和 caspase-3 的表达，激活凋亡线粒体途径。Lunasin 增加起始 caspase-9 的活性，导致 caspase-3 的激活，还修饰了人细胞外基质和黏附基因的表达，下调整合素 α(5)、SELE、MMP10、整合素 β(2) 和 COL6A1 的表达分别为 5.01、6.53、7.71、8.19 和 10.10 倍，同时上调 COL12A1 的表达为 11.61 倍。