The flavonoid apigenin upregulates CD26/DPPIV on human colorectal carcinoma cells
Date
2015-04-28
Authors
Lefort, Emilie
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Abstract
CD26/dipeptidyl peptidase IV is a cell-surface glycoprotein expressed by various cell types, including epithelial cells of the normal human colon. CD26 levels increase during epithelial cell differentiation but become dysregulated during malignancies such as colorectal cancer (CRC). CD26 depletion appears to contribute to the aggressive and metastatic phenotype of solid tumours via enhanced concentrations of the nucleoside adenosine and of the chemokine CXCL12. Apigenin (4?,5,7-trihydroxyflavone) is a flavonoid present in various fruits, vegetables and herbs, but is most abundant in the leafy herb parsley and dried flowers of chamomile. Apigenin interferes with several molecular targets implicated in cancer progression, although its effect has never been investigated in the context of CD26. In the present study we aimed to determine the effect of apigenin and other flavonoids on the multiple functions of CD26 (dipeptidyl peptidase activity, capture of ecto-adenosine deaminase and binding to cellular fibronectin) in a variety of human CRC cells. The effect of apigenin on CD26 was also evaluated in combination with current chemotherapeutic agents employed in the management of metastatic CRC. We have demonstrated that apigenin, alone and in combination with chemotherapeutic agents, increases cell-surface CD26 and its multiple functions in a way that would oppose tumour progression. Our work has further revealed a novel and highly selective topoisomerase I-dependent pathway in CRC cells that is activated by apigenin and which elevates cell-surface CD26 in a way that shows a unique interaction with the topoisomerase I inhibitor irinotecan. We therefore suggest that apigenin may be able to act alone and in conjunction with irinotecan, to modulate the metastatic phenotype of CRC cells and alter colon cancer progression.
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Keywords
Apigenin, flavonoid, colorectal cancer, CD26, Dipeptidyl peptidase IV