Apigenin inhibits HeLa sphere-forming cells through inactivation of casein kinase 2α.

The protein kinase casein kinase 2 (CK2) has been implicated in stem cell maintenance and its aberrant activation has been demonstrated in several types of cancer, including cervical cancer. In the present study, it was demonstrated that the sphere-forming cells (SFCs) of HeLa cell lines exhibited self-renewal capacity, indicating that they possessed the properties of cervical cancer stem-like cells. HeLa-derived SFCs exhibited a higher level of CK2 protein, compared with the parental cells. Apigenin, a dietary flavonoid, led to a dose-dependent inhibition of the self-renewal capacity and the protein expression of CK2 in HeLa-derived SFCs. Furthermore, forced overexpression of CK2 resulted in a decrease in the inhibition of CK2 expression and the self-renewal capacity induced by apigenin in HeLa-derived SFCs. These results suggested that apigenin inhibits the self-renewal capacity of HeLa-derived SFCs through downregulation of CK2 expression.