Display options
Cite
Yu Y, Xie Y, Cao L, et al. The ferroptosis inducer erastin enhances sensitivity of acute myeloid leukemia cells to chemotherapeutic agents. Mol Cell Oncol. 2015;2(4):e1054549doi: 10.1080/23723556.2015.1054549.
Yu, Y., Xie, Y., Cao, L., Yang, L., Yang, M., Lotze, M. T., Zeh, H. J., Kang, R., & Tang, D. (2015). The ferroptosis inducer erastin enhances sensitivity of acute myeloid leukemia cells to chemotherapeutic agents. Molecular & cellular oncology, 2(4), e1054549. https://doi.org/10.1080/23723556.2015.1054549
Yu, Yan, et al. "The ferroptosis inducer erastin enhances sensitivity of acute myeloid leukemia cells to chemotherapeutic agents." Molecular & cellular oncology vol. 2,4 (2015): e1054549. doi: https://doi.org/10.1080/23723556.2015.1054549
Yu Y, Xie Y, Cao L, Yang L, Yang M, Lotze MT, Zeh HJ, Kang R, Tang D. The ferroptosis inducer erastin enhances sensitivity of acute myeloid leukemia cells to chemotherapeutic agents. Mol Cell Oncol. 2015 May 26;2(4):e1054549. doi: 10.1080/23723556.2015.1054549. eCollection 2015. PMID: 27308510; PMCID: PMC4905356.
Copy Download .nbib Format: NLM
Share it on

Mol Cell Oncol. 2015 May 26;2(4):e1054549. doi: 10.1080/23723556.2015.1054549. eCollection 2015.

The ferroptosis inducer erastin enhances sensitivity of acute myeloid leukemia cells to chemotherapeutic agents.

Molecular & cellular oncology

Yan Yu, Yangchun Xie, Lizhi Cao, Liangchun Yang, Minghua Yang, Michael T Lotze, Herbert J Zeh, Rui Kang, Daolin Tang

Affiliations

  1. Center for DAMP Biology; Department of Surgery; University of Pittsburgh Cancer Institute; University of Pittsburgh; Pittsburgh, PA, USA; Department of Pediatrics; Xiangya Hospital; Central South University; Changsha, Hunan, China.
  2. Center for DAMP Biology; Department of Surgery; University of Pittsburgh Cancer Institute; University of Pittsburgh ; Pittsburgh, PA, USA.
  3. Department of Pediatrics; Xiangya Hospital; Central South University ; Changsha, Hunan, China.

PMID: 27308510 PMCID: PMC4905356 DOI: 10.1080/23723556.2015.1054549

Abstract

Acute myeloid leukemia (AML) is the most common type of leukemia in adults. Development of resistance to chemotherapeutic agents is a major hurdle in the effective treatment of patients with AML. The quinazolinone derivative erastin was originally identified in a screen for small molecules that exhibit synthetic lethality with expression of the RAS oncogene. This lethality was subsequently shown to occur by induction of a novel form of cell death termed ferroptosis. In this study we demonstrate that erastin enhances the sensitivity of AML cells to chemotherapeutic agents in an RAS-independent manner. Erastin dose-dependently induced mixed types of cell death associated with ferroptosis, apoptosis, necroptosis, and autophagy in HL-60 cells (AML, NRAS_Q61L), but not Jurkat (acute T-cell leukemia, RAS wild type), THP-1 (AML, NRAS_G12D), K562 (chronic myelogenous leukemia, RAS wild type), or NB-4 (acute promyelocytic leukemia M3, KRAS_A18D) cells. Treatment with ferrostatin-1 (a potent ferroptosis inhibitor) or necrostatin-1 (a potent necroptosis inhibitor), but not with Z-VAD-FMK (a general caspase inhibitor) or chloroquine (a potent autophagy inhibitor), prevented erastin-induced growth inhibition in HL-60 cells. Moreover, inhibition of c-JUN N-terminal kinase and p38, but not of extracellular signal-regulated kinase activation, induced resistance to erastin in HL-60 cells. Importantly, low-dose erastin significantly enhanced the anticancer activity of 2 first-line chemotherapeutic drugs (cytarabine/ara-C and doxorubicin/adriamycin) in HL-60 cells. Collectively, the induction of ferroptosis and necroptosis contributed to erastin-induced growth inhibition and overcame drug resistance in AML cells.

Keywords: AML; autophagy; erastin; ferroptosis; necroptosis

References

  1. Nat Rev Drug Discov. 2014 Nov;13(11):828-51 - PubMed
  2. Mol Genet Metab. 2015 Mar;114(3):397-402 - PubMed
  3. Cell. 2012 May 25;149(5):1060-72 - PubMed
  4. Blood. 1991 Mar 1;77(5):1080-6 - PubMed
  5. Curr Opin Hematol. 2014 Mar;21(2):87-94 - PubMed
  6. Cancer Cell. 2003 Mar;3(3):285-96 - PubMed
  7. Nature. 2015 Jan 15;517(7534):311-20 - PubMed
  8. Nature. 2007 Jun 14;447(7146):864-8 - PubMed
  9. Cell Death Differ. 2015 Jan;22(1):58-73 - PubMed
  10. J Biol Chem. 2013 Apr 26;288(17):11920-9 - PubMed
  11. Nat Cell Biol. 2014 Dec;16(12):1180-91 - PubMed
  12. Oncogene. 2004 Apr 12;23(16):2838-49 - PubMed
  13. Leukemia. 2015 Apr;29(4):760-9 - PubMed
  14. Cancer Chemother Rep. 1973 Nov-Dec;57(4):485-8 - PubMed
  15. Cell Metab. 2011 Jun 8;13(6):701-11 - PubMed
  16. Elife. 2014 May 20;3:e02523 - PubMed
  17. J Exp Med. 2015 Apr 6;212(4):555-68 - PubMed
  18. Curr Hematol Malig Rep. 2014 Jun;9(2):93-9 - PubMed
  19. Cell. 2014 Jan 16;156(1-2):317-31 - PubMed
  20. N Engl J Med. 2014 Jan 30;370(5):455-65 - PubMed
  21. Oncogene. 2015 Nov 5;34(45):5617-25 - PubMed
  22. J Clin Oncol. 2008 Oct 1;26(28):4603-9 - PubMed
  23. Oncol Rep. 2013 Apr;29(4):1459-66 - PubMed
  24. Toxicol Pathol. 2007 Jun;35(4):495-516 - PubMed
  25. Nat Rev Immunol. 2013 Sep;13(9):679-92 - PubMed
  26. N Engl J Med. 1997 Oct 9;337(15):1021-8 - PubMed
  27. Autophagy. 2011 Jan;7(1):112-4 - PubMed
  28. Proc Natl Acad Sci U S A. 2014 Nov 25;111(47):16836-41 - PubMed
  29. Leukemia. 2015 Mar;29(3):517-25 - PubMed
  30. Chem Biol. 2008 Mar;15(3):234-45 - PubMed
  31. Nat Rev Immunol. 2014 Nov;14 (11):759-67 - PubMed
  32. Blood. 2000 Sep 1;96(5):1655-69 - PubMed

Publication Types