Abstract
Glucocorticoids are well-known apoptotic agents in certain classes of lymphoid cell malignancies. Reduction of intracellular polyamine levels by use of inhibitors that block polyamine synthesis slows or inhibits growth of many cells in vitro. Several such inhibitors have shown efficacy in clinical trials, though the toxicity of some compounds has limited their usefulness. We have tested the effects of combinations of the glucocorticoid dexamethasone (Dex) and two polyamine inhibitors, difluoromethylornithine (DFMO) and methyl glyoxal bis guanylhydrazone (MGBG), on the clonal line of human acute lymphoblastic leukemia cells, CEM-C7-14. Dex alone kills these cells, though only after a delay of at least 24 hours. We also evaluated a partially glucocorticoid-resistant c-Myc-expressing CEM-C7-14 clone. We show that Dex downregulates ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine synthesis. Pretreatment with the ODC inhibitor DFMO, followed by addition of Dex, enhances steroid-evoked kill slightly. The combination of pretreatment with sublethal concentrations of both DFMO and the inhibitor of S-adenosylmethionine decarboxylase, MGBG, followed by addition of Dex, results in strong synergistic cell kill. Both the ...Continue Reading
References
Feb 1, 1979·Journal of Cellular Physiology·J M HarmonE B Thompson
Aug 1, 1991·Annals of Medicine·J JänneP Leinonen
Apr 1, 1988·Japanese Journal of Cancer Research : Gann·S NakaikeK Igarashi
Jan 1, 1984·Annual Review of Biochemistry·C W Tabor, H Tabor
Feb 1, 1983·Cancer Letters·P SeppänenJ Jänne
Jan 1, 1983·General Pharmacology·J Z Byczkowski, C W Porter
Aug 1, 1995·The Journal of Experimental Medicine·N ZamzamiG Kroemer
May 25, 1995·Nucleic Acids Research·T D LittlewoodG I Evan
Jul 1, 1994·Annals of Oncology : Official Journal of the European Society for Medical Oncology·D D Von Hoff
Dec 1, 1994·International Archives of Allergy and Immunology·R A Schwartzman, J A Cidlowski
Aug 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·C Bello-FernandezJ L Cleveland
Aug 1, 1996·The International Journal of Biochemistry & Cell Biology·N SeilerJ P Moulinoux
Jan 26, 1996·Journal of Chromatography. B, Biomedical Applications·S Merali, A B Clarkson
May 1, 1997·Analytical Biochemistry·T WeissH Zirngibl
Apr 1, 1997·The Journal of Steroid Biochemistry and Molecular Biology·B H JohnsonE B Thompson
Apr 29, 1998·Annual Review of Physiology·K L King, J A Cidlowski
Apr 29, 1998·Annual Review of Physiology·G KroemerM Resche-Rigon
Oct 1, 1998·Biochemical and Biophysical Research Communications·E GrassilliM A Desiderio
Apr 27, 1999·The International Journal of Biochemistry & Cell Biology·L M Shantz, A E Pegg
Oct 8, 1999·Trends in Endocrinology and Metabolism : TEM·E B Thompson
Jun 16, 2000·Journal of Immunological Methods·D A BradburyS P Crouch
Nov 9, 2000·The Journal of Steroid Biochemistry and Molecular Biology·F ZhouE B Thompson
Aug 11, 2001·Oncogene·R D MedhE B Thompson
Apr 1, 1965·Cancer·G E FOLEYR E MCCARTHY
Citations
Jun 5, 2003·Genomics·Rheem D MedhE Brad Thompson
Nov 30, 2007·Cancer Cell International·Aaron L MillerE Brad Thompson
Apr 4, 2006·Amino Acids·G BjelakovicG Kocic
May 6, 2014·Cancer Cell International·Aaron L MillerE Brad Thompson
Feb 20, 2010·Amino Acids·G BjelakovićLj Bjelakovic
Sep 24, 2004·International Journal of Cancer. Journal International Du Cancer·Eun-Joo NohBon-Hong Min
Oct 6, 2005·Journal of Cellular and Molecular Medicine·Nikolaus Seiler, Francis Raul
May 8, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Heui-Young RyuDavid H Sherr
Aug 30, 2018·Cell Death & Disease·Matheus DyczynskiRoland Nilsson
Mar 30, 2018·Molecular and Cellular Endocrinology·M S WebbE B Thompson
Aug 29, 2003·The Journal of Steroid Biochemistry and Molecular Biology·M Scott WebbE Brad Thompson