Inhibition of CK2α and PI3K/Akt synergistically induces apoptosis of CD34+CD38- leukaemia cells while sparing haematopoietic stem cells

June Won Cheong, Yoo Hong Min, Jun In Eom, Soo Jeong Kim, Hoi Kyung Jeung, Jin Seok Kim

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Background/Aim: The CD34+CD38- leukaemia cell population contains leukaemia stem cells (LSCs) responsible for treatment failure in acute myeloid leukaemia (AML) and, thus, novel therapies are required to eradicate LSCs without harming healthy haematopoietic stem cells (HSC). Materials and Methods: The present study evaluated the effects of co-treatment with LY294002 (a PI3K/Akt inhibitor) and apigenin (a CK2 inhibitor) (LY/Api) at subtoxic concentrations on leukaemia cell lines and primary AML cells. Results: LYIApi synergistically induced apoptosis in leukaemia cells, especially CD34+CD38- leukaemia cells. However, these effects were negligible in HSCs. LY/Api-induced apoptosis was accompanied by activation of caspase cascades and disruption of mitochondrial membrane potential. Caspase inhibitor or Akt overexpression abrogated this synergistic induction in apoptosis by LYIApi. LYIApi also led to remarkable down-regulation of anti-apoptotic proteins including Bcl-xL and NF-κB in CD34 +CD38- leukaemia cells, but not in healthy hematopoietic stem cells. Conclusion: Inhibition of both CK2 and PI3K/Akt pathways may be a promising LSCs-targeted therapeutic strategy for AML.

Original languageEnglish
Pages (from-to)4625-4634
Number of pages10
JournalAnticancer research
Volume30
Issue number11
Publication statusPublished - 2010 Nov 1

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Hematopoietic Stem Cells
Phosphatidylinositol 3-Kinases
Leukemia
Apoptosis
Acute Myeloid Leukemia
Stem Cells
Apigenin
Apoptosis Regulatory Proteins
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Caspase Inhibitors
Mitochondrial Membrane Potential
Myeloid Cells
Caspases
Treatment Failure
Down-Regulation
Cell Line
Therapeutics
Population

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Cheong, June Won ; Min, Yoo Hong ; Eom, Jun In ; Kim, Soo Jeong ; Jeung, Hoi Kyung ; Kim, Jin Seok. / Inhibition of CK2α and PI3K/Akt synergistically induces apoptosis of CD34+CD38- leukaemia cells while sparing haematopoietic stem cells. In: Anticancer research. 2010 ; Vol. 30, No. 11. pp. 4625-4634.
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Inhibition of CK2α and PI3K/Akt synergistically induces apoptosis of CD34+CD38- leukaemia cells while sparing haematopoietic stem cells. / Cheong, June Won; Min, Yoo Hong; Eom, Jun In; Kim, Soo Jeong; Jeung, Hoi Kyung; Kim, Jin Seok.

In: Anticancer research, Vol. 30, No. 11, 01.11.2010, p. 4625-4634.

Research output: Contribution to journalArticle

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