Cyanidin‐3‐glucoside binds to talin and modulates colon cancer cell adhesions and 3D growth

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,...

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Bibliographic Details
Published in:The FASEB journal 2020-02, Vol.34 (2), p.2227-2237
Main Authors: Baster, Zbigniew, Li, Liqing, Kukkurainen, Sampo, Chen, Jing, Pentikäinen, Olli, Győrffy, Balázs, Hytönen, Vesa P., Zhu, Haining, Rajfur, Zenon, Huang, Cai
Format: Article
Language:English
Subjects:
adhesion
Animals
Anthocyanins - pharmacokinetics
cancer prevention
Cell Adhesion - drug effects
Cell Culture Techniques
Cell Proliferation - drug effects
CHO Cells
Colonic Neoplasms - chemistry
Colonic Neoplasms - metabolism
Colonic Neoplasms - pathology
Cricetinae
Cricetulus
cyanidin‐3‐glucoside
drug discovery
Glucosides - pharmacokinetics
HCT116 Cells
Humans
molecular docking
Molecular Dynamics Simulation
Neoplasm Proteins - chemistry
Neoplasm Proteins - metabolism
Talin - chemistry
Talin - metabolism
talin1
talin2
β‐integrin
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Summary: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.
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.201900945R