Lunasin induces apoptosis and modifies the expression of genes associated with extracellular matrix and cell adhesion in human metastatic colon cancer cells
Lunasin induces apoptosis and modifies the expression of genes associated with extracellular matrix and cell adhesion in human metastatic colon cancer cells
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DOI：
10.1002/mnfr.201000419
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发表时间：
2011-04-01
影响因子：
5.2
通讯作者：
de Mejia, Elvira Gonzalez
中科院分区：
文献类型：
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作者：
Dia, Vermont P.;de Mejia, Elvira Gonzalez
用途：新月菌素是一种精氨酸-甘氨酸-天冬氨酸(RGD)抗癌多肽。目的：探讨新月菌素诱导人结肠癌细胞及其奥沙利铂耐药变异体细胞凋亡的作用及其对细胞外基质和黏附基因表达的影响。方法与结果：采用流式细胞仪和荧光显微镜技术对不同转移的人结肠癌细胞株进行体外检测。LUNASIN对不同结肠癌细胞的杀伤作用与α(5)β(1)整合素的表达有关，对KM12L4细胞的杀伤作用最强(IC50=13mM)。LUNASIN使细胞周期停滞于G2/M期，并伴随着细胞周期蛋白依赖性激酶抑制因子p21和p27表达的增加。在KM12L4和KM12L4-OxR细胞中，LUNASIN(5-25MU M)激活了线粒体的凋亡途径，表现为Bcl2、Bax、核聚集素、细胞色素c和caspase-3表达的变化。LUNASIN可增强caspase-9启动子活性，激活caspase-3，并改变人细胞外基质和黏附基因的表达，使整合素α(5)、SELE、MMP10、整合素β(2)和COL6A1分别下调5.01倍、6.53倍、7.71倍、8.19倍和10.10倍，上调COL12A1基因11.61倍。
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 alpha(5)beta(1) integrin, being most potent to KM12L4 cells (IC50 = 13 mu M). 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 mu M) 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 alpha(5), SELE, MMP10, integrin beta(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.