Markey Cancer Center, Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY, USA.
Institute of Physics, Faculty of Physics, Astronomy and Applied Computer Science, Jagiellonian University, Krakow, Poland.
FASEB J. 2020 Feb;34(2):2227-2237. doi: 10.1096/fj.201900945R. Epub 2020 Jan 9.
Cyanidin-3-glucoside (C3G) is a natural pigment, found in many colorful fruits and vegetables. It has many health benefits, including anti-inflammation, cancer prevention, and anti-diabetes. Although C3G is assumed to be an antioxidant, it has been reported to affect cell-matrix adhesions. However, the underlying molecular mechanism is unknown. Here, we show that the expression of talin1, a key regulator of integrins and cell adhesions, negatively correlated with the survival rate of colon cancer patients and that depletion of talin1 inhibited 3D spheroid growth in colon cancer cells. Interestingly, C3G bound to talin and promoted the interaction of talin with β1A-integrin. Molecular docking analysis shows that C3G binds to the interface of the talin-β-integrin complex, acting as an allosteric regulator and altering the interaction between talin and integrin. Moreover, C3G promoted colon cancer cell attachment to fibronectin. While C3G had no significant effect on colon cancer cell proliferation, it significantly inhibited 3D spheroid growth in fibrin gel assays. Since C3G has no or very low toxicity, it could be potentially used for colon cancer prevention or therapy.
矢车菊素-3-葡萄糖苷（C3G）是一种天然色素，存在于许多色彩鲜艳的水果和蔬菜中。它有许多健康益处，包括抗炎、防癌和抗糖尿病。尽管 C3G 被认为是一种抗氧化剂，但它已被报道会影响细胞-基质黏附。然而，其潜在的分子机制尚不清楚。在这里，我们表明，作为整合素和细胞黏附的关键调节剂的 talin1 的表达与结肠癌患者的存活率呈负相关，并且 talin1 的耗竭抑制了结肠癌细胞的 3D 球体生长。有趣的是，C3G 与 talin 结合并促进了 talin 与β1A-整合素的相互作用。分子对接分析表明，C3G 结合到 talin-β-整合素复合物的界面上，作为别构调节剂改变 talin 和整合素之间的相互作用。此外，C3G 促进了结肠癌细胞与纤维连接蛋白的黏附。虽然 C3G 对结肠癌细胞的增殖没有显著影响，但它显著抑制了纤维蛋白凝胶测定中的 3D 球体生长。由于 C3G 没有或只有很低的毒性，它可能被潜在地用于结肠癌的预防或治疗。
