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

Abstract

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. K E Y W O R D Sadhesion, cancer prevention, cyanidin-3-glucoside, drug discovery, molecular docking, talin1, talin2, β-integrin 2228 | BASTER ET Al. | 2229BASTER ET Al. | Cell proliferation assaysCells were trypsinized and resuspended in DMEM containing 10% FBS at a density of 5 × 10 4 cells/mL. Cells were treated with C3G or vehicle (DMSO) where was indicated. One hundred microliters of cells was added to each well of 96-well tissue culture plates. The cells were allowed to grow for 1-4 days (as indicated) in a CO2 incubator and then incubated with 10 µL (per well) of TetraZ (WST-8) cell counting kit. Cell proliferation was determined by measuring absorbance 450 nm using a BioTek plate reader.

The mechanisms of wine phenolic compounds for preclinical anticancer therapeutics

“…A study shows that C3G could be potentially used for the prevention or therapy of colon cancer. This study also reveals that C3G exerts its effect by binding to talin and promoting the interaction of talin with β1A-integrin, which negatively correlates to the survival rate of patients with colon cancer ( 92 ). At concentrations of 25–100 μM, Cyanidin-3-O-glucoside (C3G) inhibits the proliferation of renal cell carcinoma cells and tumorigenesis by arresting the cell cycle, inducing apoptosis and autophagy by regulating the expression of early growth response protein 1 (EGR1), selenoprotein W1 (SEPW1), p62 or sequestosome 1, and autophagy related gene 4 (ATG4) ( 93 ).…”

Anthocyanins in Colorectal Cancer Prevention Review

“…Moreover, cyanidin-3-glucoside had the best antioxidant effects among the anthocyanins and other phenolics extracted from strawberries [77]. The cyanidin-3-glucoside single component promoted colon cancer cell attachment to fibronectin and inhibited 3D spheroid growth [78]. Cyanidin-3-Oβ-glucoside extracted from purple corn can decrease the development of colonic mucosal lesions and ACF induction in DMH-PhIP-treated animals [79].…”

Phytochemicals in Cancer Immune Checkpoint Inhibitor Therapy

“…Cyanidin 3-O-glucoside (C3G) is an anthocyanin extracted from many fruits and vegetables. C3G is beneficial to the human body through antioxidant or anti-tumorigenic effects [134][135][136][137]. However, there is not much research on how C3G can affect the immune response.…”