Flavones and Flavonols may have Clinical Potential as CK2 Inhibitors in Cancer Therapy

Mark F. McCarty*

Flavones and Flavonols may have Clinical Potential as CK2 Inhibitors in Cancer Therapy.
The serine-threonine kinase CK2, which targets over 300 cellular proteins, is over expressed in all cancers, presumably reflecting its ability to promote proliferation, spread, and survival through a wide range of complementary mechanisms.

Via an activating phosphorylation of Cdc373, a co-chaperone which partners with Hsp90, CK2 prolongs the half-life of protein kinases that promote proliferation and survival in many cancers, including Akt, Src, EGFR, Raf-1, and several cyclin-dependent kinases. CK2 works in other ways to boost the activity of signaling pathways that promote cancer aggressiveness and chemo resistance, including those driven by Akt, NF-kappaB, hypoxia-inducible factor-1, beta-catenin, STAT3, hedgehog, Notch1, and the androgen receptor; it also promotes the epidermal-mesenchymal transition and aids efficiency of DNA repair.

CX-4945 has shown impressive activity in cell culture studies and xenograft models, and is now entering clinical trials. Moreover, it has long been recognized that the natural flavone apigenin can inhibit CK2, with a Ki near 1 micromolar; more recent work indicates that a range of flavones and flavanols, characterized by a planar structure and hydroxylations at the 7 and 4’ positions – including apigenin, luteolin, keampferol, fisetin, quercetin, and myricetin – can inhibit CK2 with Ki s in the sub-micromolar range.

It is reasonable to suspect that, at least in physiologically achievable concentrations, these agents may be achieving these effects primarily via CK2 inhibition. Inefficient absorption and rapid conjugation limit the bio efficacy of orally administered flavonoids.

Cancer Stud Mol Med Open J. 2015; 2(1): 39-51. doi: 10.17140/CSMMOJ-2-105