Apigenin inhibits the self-renewal capacity of human ovarian cancer SKOV3‑derived sphere-forming cells

Mol Med Rep. 2015 Mar;11(3):2221-6. doi: 10.3892/mmr.2014.2974. Epub 2014 Nov 18.


Casein kinase 2 (CK2) is a protein kinase which is frequently activated in cancer. The Hedgehog (Hh) signaling pathway is involved in the stimulation of cancer stem cell growth. Its aberrant activation has been validated in several types of cancer, including ovarian cancer. In the present study, the sphere‑forming cells (SFCs) of the human ovarian cancer SKOV3 cell line were observed to have self‑renewal capacity, indicating the possession of ovarian cancer stem‑like cell properties. SKOV3‑derived SFCs had higher levels of CK2α and glioma‑associated oncogene 1 (Gli1) proteins compared with those of parental cells. Apigenin, a common flavonoid, significantly inhibited the self‑renewal capacity and the protein expression of CK2α and Gli1 proteins in the SKOV3‑derived SFCs, which occurred in a concentration‑dependent manner. In addition, CK2α small interfering RNA downregulated the protein expression of CK2α and Gli1 and synergistically inhibited the self‑renewal capacity of the SKOV3‑derived SFCs with apigenin. However, forced overexpression of CK2α resulted in an increase in the expression of CK2α and Gli1 and attenuated the apigenin‑inhibited self‑renewal effect in the SKOV3‑derived SFCs. These results suggested that apigenin inhibited the self‑renewal capacity of SKOV3‑derived SFCs and was involved in downregulating the expression of Gli1 by the inhibition of CK2α.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apigenin / pharmacology*
  • Casein Kinase II / genetics
  • Casein Kinase II / metabolism
  • Cell Line, Tumor
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / metabolism*
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • Spheroids, Cellular
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Tumor Cells, Cultured
  • Zinc Finger Protein GLI1


  • Antineoplastic Agents
  • Oncogene Proteins
  • Trans-Activators
  • Zinc Finger Protein GLI1
  • Apigenin
  • Casein Kinase II