Journal of Inorganic Biochemistry, 2013, 127C(29):107-115.

Effects of chrysin, apigenin, genistein and their homoleptic copper(II) complexes on the growth and metastatic potential of cancer cells

Cornelia Spoerlein, Katharina Mahal, Holger Schmidt, et al

Organic Chemistry Laboratory, University of Bayreuth, Universitätsstraße 30, 95447 Bayreuth, Germany; Department of Plant Physiology, University of Bayreuth, Universitätsstraße 30, 95447 Bayreuth, Germany

The (iso-)flavonoids chrysin 1, apigenin 2, genistein 3 and their homoleptic copper(II) complexes 4-6 were compared for general cancer cell growth inhibition and for antimetastatic effects on rapidly proliferating and metastasizing 518A2 melanoma cells. The complexes 4-6 were three to five times more active than the free flavonoids in cytotoxicity assays with MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] against 518A2 melanoma, HCT-116 colon, KB-V1/Vbl cervix, and MCF-7/Topo breast carcinoma cells. This activity correlated with an arrest of the cell cycle of 518A2 melanoma cells at the G2/M transition. The complexes also diminished the migration propensity of these cells in wound healing assays more distinctly than the flavonoid ligands. By fluorescent staining of F-actin and beta-catenin the antimetastatic effects of the Cu(II) genistein complex 6 were shown to originate from a remodeling of the actin cytoskeleton and an increase in cadherin-catenin complex formation, factors that favor cell-cell adhesion. Complex 6 also attenuated the expression and secretion of the metastasis-relevant matrix metalloproteinases MMP-2 and MMP-9. In summary, coordination of apigenin and genistein to Cu(II) greatly enhances the antitumoral properties of these flavonoids and potentiates their mechanistic diversity.

美国《无机生物化学杂志》，2013年10月

白杨素、 芹菜素、 金雀异黄素及其铜（II）配合物对癌细胞生长和侵袭转移潜能的影响

科妮莉亚 斯珀尔琳，卡塔琳娜 玛哈尔，霍尔格  施密特，等

德国拜罗伊特大学有机化学实验室和植物生理学院

（异）黄酮类化合物白杨素1、 芹菜素 2、 金雀异黄素 3 和他们铜（II）配合物 4-6被用来比较一般的癌症细胞生长的抑制作用和对518A2 黑色素瘤细胞迅速增殖和转移的影响。在细胞毒性实验中，在用MTT法对抗 518A2 黑色素瘤、 HCT 116 结肠、 KB-V1/Vbl 宫颈和 MCF-7/Topo 乳腺癌细胞时，配合物 4-6 是黄酮类化合物活性的三到五倍。这一活性与518A2 黑素瘤细胞周期的G2/M 期的阻滞相关。在创面愈合实验中，配合物同样比黄酮类化合物更明显地减少了这些细胞的迁移倾向。通过F-肌动蛋白和 β-连环蛋白的荧光染色法发现Cu(II)金雀异黄素配合物的抗迁移影响源于肌动蛋白细胞骨架的重构和增加钙黏蛋白复合形式的增加，有利于细胞间的粘附。配合物 6 也会减弱与迁移有关的基质金属蛋白酶-2 和基质金属蛋白酶-9 的表达和分泌。总之，芹菜素和金雀异黄素与二价铜的配合物大大提高了这些黄酮类化合物的抗肿瘤特性，并增强其多样性。