Abstract
CD26/DPPIV is a cell surface glycoprotein found on cells of the intestinal epithelium including those of the colon. We have previously shown that the dietary flavone apigenin (4′,5,7‐trihydroxyflavone) upregulates CD26/DPPIV on colon cells. Flavonoids such as apigenin interfere with the action of multiple cellular protein kinases and have the capacity to modulate the cell exterior and its ability to interface with the local environment through different signaling pathways. We show here that the ability of apigenin to upregulate CD26/DPPIV is exerted through and requires the activity of casein kinase 2 (CK2). Inhibitors of CK2 that are distinct from apigenin (emodin, 6‐methyl‐1,3,8‐trihydroxyanthraquinone; TBB, 4,5,6,7‐tetrabromobenzotriazole; and DRB, 5,6‐dichlorobenzimidazole 1‐β‐D‐ribofuranoside) showed a dose‐dependent ability to increase CD26/DPPIV and had the same maximal effect when combined with apigenin at submaximal concentrations. Knockdown of CK2 with siRNA abrogated the ability of apigenin to upregulate CD26/DPPIV. Apigenin treatment of cells had no effect on the levels of CK2 protein, consistent with an inhibition of activity of the enzyme. Apigenin's upregulation of CD26/DPPIV in differentiated human colon epithelial cells depends upon inhibition of CK2 activity. This is a key step in enabling apigenin's ability to regulate the functions of intestinal epithelial cells.
Highlights
Apigenin (4′,5,7-trihydroxyflavone) is a flavone present in the leafy herb parsley and in the dried flowers of chamomile, among other sources
We previously documented the ability of apigenin to upregulate the cell surface expression of Cluster of differentiation marker 26 (CD26)/DPPIV on HT-29 and HRT-18 human colorectal cells (Lefort & Blay, 2011)
In addition to HRT-18 and HT-29 cells, well-differentiated Caco-2 cells showed a robust elevation in CD26/DPPIV in response to apigenin, which was an approximate doubling of CD26/DPPIV (Figure 1)
Summary
Apigenin (4′,5,7-trihydroxyflavone) is a flavone present in the leafy herb parsley and in the dried flowers of chamomile, among other sources. We show here that apigenin's ability to upregulate CD26/DPPIV requires inhibition of this key cellular kinase casein, CK2. We previously documented the ability of apigenin to upregulate the cell surface expression of CD26/DPPIV on HT-29 and HRT-18 human colorectal cells (Lefort & Blay, 2011).
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