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Rep Biochem Mol Biol. 2016 Apr;4(2):82-8.

Parthenolide Induces Apoptosis in Committed Progenitor AML Cell line U937 via Reduction in Osteopontin.

Reports of biochemistry & molecular biology

Mahdi Zahedpanah, Mojgan Shaiegan, Seyed Hamidollah Ghaffari, Mohsen Nikbakht, Mahin Nikugoftar, Saeed Mohammadi

Affiliations

  1. Blood Transfusion Research center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran.
  2. Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

PMID: 27536701 PMCID: PMC4986266

Abstract

BACKGROUND: Interfering with cell proliferation and survival is a critical role for antineoplastic drugs leading to cell death through induction of apoptosis. Alternative treatments with herbal extracts offer insights into acute myeloid leukemia (AML) therapy. Parthenolide (PTL), an extract from feverfew, induces apoptosis in primary human leukemia stem cells (LSCs) and bulk leukemic cell populations. Osteopontin (OPN) preserves cell viability in response to anticancer agents and its receptors could be utilized for therapeutic targeting of cancer cells.

METHODS: U937 cells were cultured in RPMI 1640 with concentrations of 2, 4, 6, 8, and 10 µM PTL for 20-24 hours for MTT assays. Apoptosis assays were performed with Annexin V-Alexa Fluor-488/PI as Annexin V+/PI- and Annexin V+/PI+ to measure early and late apoptosis, respectively. Quantitative real-time PCR was used to measure OPN gene expression using the 2(-ΔΔCt) method. The PTL-treated cells were stained with FITC-CD38 antibody for flow cytometry analyses. Data were compared using one-way analysis of variance (ANOVA) by SPSS 19.

RESULTS: Parthenolide inhibited growth of U937 cells with IC25 and IC50 values of 4 and 5.8 µM, respectively. Death induction with PTL was apoptotic. Flow cytometry showed a significant decrease in the percentage of CD38+ U937 cells in response to PTL. Osteopontin gene expression decreased in response to PTL.

CONCLUSION: PTL induced apoptosis and reduced OPN gene expression in U937 cells.

Keywords: AML cell line U937; Osteopontin; Parthenolide

References

  1. J Biol Chem. 2002 Oct 11;277(41):38954-64 - PubMed
  2. Arthritis Res Ther. 2014 Jan 20;16(1):R17 - PubMed
  3. Blood. 2008 Aug 1;112(3):568-75 - PubMed
  4. Trends Cell Biol. 2006 Feb;16(2):79-87 - PubMed
  5. Proc Natl Acad Sci U S A. 1997 May 13;94(10):5320-5 - PubMed
  6. J Pharmacol Exp Ther. 2010 Nov;335(2):389-400 - PubMed
  7. Blood. 2007 Dec 15;110(13):4427-35 - PubMed
  8. Cancer Immunol Immunother. 2010 Mar;59(3):355-66 - PubMed
  9. Blood. 2013 Feb 21;121(8):1384-93 - PubMed
  10. Blood. 1994 Oct 15;84(8):2672-80 - PubMed
  11. Blood. 2008 Jun 15;111(12 ):5654-62 - PubMed
  12. Blood. 2005 Jun 1;105(11):4163-9 - PubMed
  13. Naunyn Schmiedebergs Arch Pharmacol. 2015 Sep;388(9):921-30 - PubMed
  14. Int J Oncol. 2010 Nov;37(5):1307-13 - PubMed
  15. Mol Cell Biol. 1990 May;10(5):2327-34 - PubMed
  16. J Leukoc Biol. 1985 Apr;37(4):407-22 - PubMed
  17. Haematologica. 2014 Aug;99(8):1277-84 - PubMed
  18. Crit Rev Oral Biol Med. 2000;11(3):279-303 - PubMed
  19. Hematology Am Soc Hematol Educ Program. 2001;:62-86 - PubMed
  20. Clin Lab Med. 2007 Sep;27(3):551-75, vii - PubMed
  21. Bioorg Med Chem Lett. 2009 Aug 1;19(15):4346-9 - PubMed
  22. J Inflamm (Lond). 2011 Oct 12;8:26 - PubMed
  23. N Engl J Med. 1999 Sep 30;341(14):1051-62 - PubMed
  24. BMC Cancer. 2012 Oct 05;12:453 - PubMed
  25. Mol Cancer. 2007 Jan 16;6:6 - PubMed
  26. Nat Med. 1997 Jul;3(7):730-7 - PubMed
  27. J Immunol. 2011 Mar 1;186(5):3173-9 - PubMed
  28. J Cell Biochem. 2002;87(1):93-102 - PubMed
  29. Arch Pathol Lab Med. 2003 Sep;127(9):1140-7 - PubMed
  30. Folia Histochem Cytobiol. 2008;46(2):129-35 - PubMed

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