Flavonoids promote cell migration in nontumorigenic colon epithelial cells differing in Apc genotype:: Implications of matrix metalloproteinase activity
Flavonoids promote cell migration in nontumorigenic colon epithelial cells differing in Apc genotype:: Implications of matrix metalloproteinase activity
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DOI：
10.1207/s15327914nc4802_8
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发表时间：
2004-01-01
影响因子：
2.9
通讯作者：
Hord, NG
中科院分区：
文献类型：
--
作者：
Fenton, JI;Hord, NG
结肠上皮细胞迁移是向上移动到隐窝顶端所必需的，因此是正常分化细胞功能所必需的。这种迁移表型依赖于野生型腺瘤性结肠息肉病 (Apc) 的表达。本研究的目的是确定特定黄酮类化合物是否诱导野生型或 Apc 基因型杂合结肠上皮细胞的细胞迁移。使用具有不同 Apc 基因型的非致瘤性小鼠结肠上皮细胞系、年轻成年小鼠结肠 (YAMC; Apc(+/+)) 细胞和 Immortomouse/Min 结肠上皮 (IMCE; Apc(Min/+)) 细胞来评估特定黄酮类化合物相对于肝细胞生长因子 (HGF) 诱导的细胞迁移的能力。与 HGF 相比，柑橘黄烷酮柚皮素和橙皮素在任一细胞类型中均不诱导细胞迁移。然而，这些黄烷酮、柚皮苷和橙皮苷的糖基化形式在 YAMC 和 IMCE 细胞中诱导不同的迁移。具体而言，柚皮苷和橙皮苷在1μM时在IMCE细胞中诱导最大的迁移反应（P<0.01），并且诱导的迁移大于未处理的对照细胞（P<0.05），但与HGF处理的细胞相同。在 YAMC 细胞中，除非浓度为 100 μM，否则橙皮苷不会诱导迁移。芹菜素在 1 (P < 0.05) 和 50 muM (P < 0.01) 时诱导 IMCE 细胞迁移，但不诱导 YAMC 细胞迁移。儿茶素仅在最高浓度（300μM）下在IMCE细胞中诱导迁移，而表儿茶素仅在最低浓度（1μM）下在IMCE细胞中诱导迁移。总体而言，糖基化柑橘黄烷酮在 IMCE 细胞中以最低浓度诱导最大的迁移反应。在柚皮苷、橙皮苷或芹菜素存在的情况下，用整体基质金属蛋白酶 (MMP) 抑制剂 Ilomastat(R) 共同处理 IMCE 细胞，结果表明类黄酮诱导的迁移依赖于 MMP 活性。在这些肿瘤前上皮细胞模型中，类黄酮诱导迁移表型表明了预防结肠癌的新机制。
Colonic epithelial cell migration is required for movement up to the apex of the crypt and, hence, normal differentiated cell function. This migratory phenotype is dependent upon wild-type adenomatous polyposis coli (Apc) expression. The purpose of this study is to determine whether specific flavonoids induce cell migration in colon epithelial cells either wild type or heterozygous for Apc genotype. Nontumorigenic murine colon epithelial cell lines with distinct Apc genotypes, young adult mouse colon (YAMC; Apc(+/+)) cells, and Immortomouse/Min colon epithelial (IMCE; Apc(Min/+)) cells were used to assess the ability of specific flavonoids to induce cell migration relative to migration induced by hepatocyte growth factor (HGF). The citrus flavanones naringenin and hesperetin did not induce cell migration comparable with HGF in either cell type. However, the glycosylated forms of these flavanones, naringin and hesperidin, induced migration differentially in YAMC and IMCE cells. Specifically, naringin and hesperidin induced the greatest migratory response in IMCE cells at 1 muM (P < 0.01) and induced migration greater than untreated control cells (P < 0.05) but equal to HGF-treated cells. In YAMC cells, hesperidin did not induce migration except at the 100-muM concentration. Apigenin induced migration in IMCE cells at 1 (P < 0.05) and 50 muM (P < 0.01) and did not induce migration in the YAMC cells. Catechin induced migration at the highest concentration (300 muM) only in the IMCE cells, whereas epicatechin induced migration at the lowest concentration only (1 muM) in IMCE cells. Overall, the glycosylated citrus flavanones induced the greatest migratory response at the lowest concentration in IMCE cells. Co-treatment Of IMCE cells with the global matrix metalloproteinase (MMP) inhibitor Ilomastat(R) in the presence of naringin, hesperidin, or apigenin demonstrated that flavonoid-induced migration was dependent on MMP activity. Induction of the migratory phenotype by flavonoids in these models of preneoplastic epithelial cells suggests a novel mechanism for colon cancer prevention.