Actions of the Dietary Flavone Apigenin in the Context of Human Colorectal Cancer

Apigenin (4′,5,7-trihydroxyflavone) is a flavone present in plant sources such as the leafy herb parsley and in the dried flowers of chamomile. We have observed that apigenin has a broad spectrum of activities that may be beneficial in the context of gastrointestinal cancers. In particular, it can inhibit several steps of the malignant process relating to tissue hypoxia, invasion of the extracellular matrix, and intracellular signalling through protein kinases. In addition we have recently shown that it can upregulate a cell-surface protein on human colorectal cancer cells termed CD26 that has been implicated in the dissemination of the cancer through metastasis. We consider CD26 to be a key regulator of cell activity as it is at an intersection of several important pathways including those involved in nucleoside regulation and the cleavage of bioactive peptides. The effect of apigenin seems to focus on CD26 as we do not see changes in other cell-surface proteins relating to nucleoside metabolism or biopeptide cleavage. In terms of apigenin's ability to alter cell biochemistry it is best known as an inhibitor of casein kinase 2 (CK2). However, we find that the apigenin regulation of CD26 is not explained by CK2 inhibition and may follow from further actions such as inhibition of MAP kinases or novel effects on pathways that affect DNA topoisomerase enzymes. Apigenin stands out amongst natural products that are of interest for their possible therapeutic activities, in that although it has the multiple cellular actions we expect from small molecules with limited informational content, its particular impacts on cell biochemistry constitute a unique set of influences that may fortuitously combine to have benefits in reducing colorectal cancer progression and metastasis.