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Tumor Biology

, Volume 37, Issue 8, pp 11001–11006 | Cite as

Valproic acid may exerts its cytotoxic effect through rassf1a expression induction in acute myeloid leukemia

  • Zare-Abdollahi Davood
  • Safari Shamsi
  • Hamid Ghaedi
  • Riazi-Isfahani Sahand
  • Ghadyani Mojtaba
  • Tabarraee Mahdi
  • Mirfakhraie Reza
  • Mohammad Javad Ebrahimi
  • Reyhaneh Sadat Miri-Moosavi
  • Sara Boosaliki
  • Omrani Mir Davood
Original Article

Abstract

In acute myeloid leukemia (AML), despite the acceptance of standard intensive chemotherapy as an optimal induction regimen for all age groups, in the elderly patients, the best treatment should meet the challenge of multiple factors like age, comorbidities, and cytogenetics, making them ineligible for standard induction chemotherapy. Using the current low-intensity therapies like decitabine, azacitidine, and low-dose cytarabine as a single arm, outcomes for these patients remain poor. As a histone deacetylase inhibitor valproic acid (VPA) exhibit anticancer activity by triggering apoptosis, the mechanism of which is not yet completely clarified. To explore the possible connection between VPA treatment and the Hippo pathway as an apoptosis stimulating route, we also explore the expression of major components of this pathway and for the first time we postulate a relationship between VPA treatment and cell death induction through RASSF1A expression induction. Furthermore, we demonstrate that autophagy inhibition by chloroquine (CQ) significantly augmented the cytotoxic effect of VPA on AML cells, especially in those with unfavorable and normal karyotype. Regarding that VPA and CQ are well-tolerated drugs and our presumptive results of usefulness of VPA + CQ in three cytogenetic risk groups of AML, this combinatorial therapy could represent an attractive treatment option for older AML patients unfit for intensive therapy.

Keywords

Valproic acid VPA, chloroquine HDAC Acute myeloid leukemia AML Cytogenetics Apoptosis Autophagy BECN1 ATG7 RASSF1A MST1 MST2 

Notes

Acknowledgments

We would like to thank the patients who participated in this study.

Compliance with ethical standard

All samples were included after obtaining Institutional Review Board Approval and informing consent in accordance with the Declaration of Helsinki.

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Zare-Abdollahi Davood
    • 1
  • Safari Shamsi
    • 1
  • Hamid Ghaedi
    • 1
  • Riazi-Isfahani Sahand
    • 2
  • Ghadyani Mojtaba
    • 1
  • Tabarraee Mahdi
    • 1
  • Mirfakhraie Reza
    • 1
  • Mohammad Javad Ebrahimi
    • 1
  • Reyhaneh Sadat Miri-Moosavi
    • 3
  • Sara Boosaliki
    • 1
  • Omrani Mir Davood
    • 1
  1. 1.Faculty of Medicine, Department of Medical GeneticsShahid Beheshti University of Medical SciencesTehranIran
  2. 2.Department of Social Determinants of Health, National Institute of Health ResearchTehran University of Medical SciencesTehranIran
  3. 3.Department of Cellular and Molecular BiologyIslamic Azad University East TehranTehranIran

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