期刊
FASEB JOURNAL
卷 34, 期 2, 页码 2227-2237出版社
WILEY
DOI: 10.1096/fj.201900945R
关键词
adhesion; cancer prevention; cyanidin-3-glucoside; drug discovery; molecular docking; talin1; talin2; beta-integrin
资金
- HHS \ NIH \ National Institute of General Medical Sciences (NIGMS) [R01 GM122994]
- Faculty of Physics, Astronomy, and Applied Computer Science of Jagiellonian University [N17/MNS/000006]
- BRATNIAK Jagiellonian University Students and Graduates Foundation
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 beta 1A-integrin. Molecular docking analysis shows that C3G binds to the interface of the talin-beta-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.
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