Display options
Share it on

Cancer Microenviron. 2016 Dec;9(2):119-126. doi: 10.1007/s12307-016-0187-0. Epub 2016 Jul 25.

Investigating Effects of Acidic pH on Proliferation, Invasion and Drug-Induced Apoptosis in Lymphoblastic Leukemia.

Cancer microenvironment : official journal of the International Cancer Microenvironment Society

Mahbobeh Bohloli, Amir Atashi, Masoud Soleimani, Saeid Kaviani, Azadeh Anbarlou

Affiliations

  1. Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
  2. Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. [email protected].

PMID: 27457339 PMCID: PMC5264660 DOI: 10.1007/s12307-016-0187-0

Abstract

Some studies have shown that extracellular pH in tumors, which results in tumor progression, is less than that in normal tissues. The aim of this study was to investigate the effects of extracellular acidic pH on proliferation, invasion, and drug-induced apoptosis in acute lymphoblastic cells. The cells were cultured in different pH (pH 6.6 and pH 7.4) for 12 days. Cell proliferation was assessed by MTT assay and cell invasion was assayed by invasion assay and gene expression analysis of MMP-9. Drug-induced apoptosis was evaluated after exposure to doxorubicin for 24 hours by annexin V/PI staining and gene expression analysis of BAX pro-apoptotic protein. The results indicated the enhanced growth and invasion of leukemic cells at pH 6.6 (P ≤ 0.05). Furthermore, the cells at pH 6.6 were resistant to apoptosis by doxorubicin (P ≤ 0.05). It can be concluded that acidic pH increases the proliferation, invasion and reduces the drug-induced apoptosis in acute lymphoblastic leukemia. Extracellular acidity can influence the behavior of leukemic cells and therefore, the manipulation of extracellular liquid can be selected as a therapeutic strategy for leukemia, especially for acute lymphoblastic leukemia.

Keywords: Acidic pH; Drug-induced apoptosis; Invasion; Lymphoblastic leukemia; Proliferation

References

  1. Neoplasia. 2003 Mar-Apr;5(2):135-45 - PubMed
  2. Future Oncol. 2005 Dec;1(6):779-86 - PubMed
  3. Cell Biosci. 2014 Aug 19;4:45 - PubMed
  4. Genes Dev. 2009 Mar 1;23(5):537-48 - PubMed
  5. Clin Exp Metastasis. 2008;25(4):411-25 - PubMed
  6. Exp Oncol. 2012 Jul;34(2):79-84 - PubMed
  7. Cell Metab. 2008 Jan;7(1):11-20 - PubMed
  8. Hematol Oncol Clin North Am. 2009 Aug;23(4):655-74 - PubMed
  9. Neoplasia. 2006 Feb;8(2):143-52 - PubMed
  10. Neoplasia. 2003 Nov-Dec;5(6):533-45 - PubMed
  11. Cancer Res. 2009 Mar 15;69(6):2260-8 - PubMed
  12. J Biol Chem. 2012 Aug 31;287(36):30664-76 - PubMed
  13. Apoptosis. 2007 Mar;12 (3):573-91 - PubMed
  14. Cancer Res. 2000 Aug 15;60(16):4610-6 - PubMed
  15. Cell. 2011 Mar 4;144(5):646-74 - PubMed
  16. Altern Med Rev. 2010 Sep;15(3):264-72 - PubMed
  17. Biochem J. 2004 Jan 15;377(Pt 2):347-55 - PubMed
  18. Br J Cancer. 1999 Jun;80(7):1005-11 - PubMed
  19. Br J Haematol. 2004 Oct;127(1):3-11 - PubMed
  20. Genes Dev. 2001 Nov 15;15(22):2922-33 - PubMed
  21. Cell Death Dis. 2013 Mar 07;4:e532 - PubMed
  22. Cancer Metab. 2014 Feb 04;2(1):3 - PubMed
  23. FASEB J. 2006 May;20(7):828-32 - PubMed
  24. Mol Med. 2010 Mar;16(3-4):144-53 - PubMed
  25. J Pathol. 2013 Aug;230(4):350-5 - PubMed
  26. Cancer Cell. 2007 Apr;11(4):335-47 - PubMed
  27. Genes Dev. 2000 Jan 15;14(2):163-76 - PubMed
  28. Cancer Cell. 2008 Dec 9;14 (6):435-46 - PubMed
  29. Clin Exp Metastasis. 2011 Dec;28(8):841-9 - PubMed
  30. J Clin Pharm Ther. 2011 Jun;36(3):299-326 - PubMed
  31. Cancer Res. 2006 Jul 1;66(13):6699-707 - PubMed
  32. Cancer Res. 2009 Mar 15;69(6):2677-84 - PubMed
  33. Cancer Cell. 2012 Jul 10;22(1):9-20 - PubMed
  34. Cancer Res. 2001 Aug 15;61(16):6020-4 - PubMed
  35. Cancer Cell Int. 2013 Sep 03;13(1):89 - PubMed
  36. J Biol Chem. 2002 Mar 29;277(13):11368-74 - PubMed
  37. Cancer Res. 2012 Aug 15;72(16):3938-47 - PubMed
  38. Ann Appl Stat. 2009;3(4):1675-1694 - PubMed
  39. Nat Rev Immunol. 2008 May;8(5):380-90 - PubMed

Publication Types