2,5-Dimethyl-celecoxib inhibits cell cycle progression and induces apoptosis in human leukemia cells

The Journal of Pharmacology and Experimental Therapeutics
Cyril SobolewskiMarc Diederich

Abstract

Cyclooxygenase-2 (COX-2) is an essential regulator of cancer promotion and progression. Extensive efforts to target this enzyme have been developed to reduce growth of cancer cells for chemopreventive and therapeutic reasons. In this context, cyclooxygenase-2 inhibitors present interesting antitumor effects. However, inhibition of COX-2 by anti-COX-2 compounds such as celecoxib was recently associated with detrimental cardiovascular side effects limiting their clinical use. As many anticancer effects of celecoxib are COX-2 independent, analogs such as 2,5-dimethyl-celecoxib (DMC), which lacks COX-2-inhibitory activity, represent a promising alternative strategy. In this study, we investigated the effect of this molecule on growth of hematologic cancer cell lines (U937, Jurkat, Hel, Raji, and K562). We found that this molecule is able to reduce the growth and induces apoptosis more efficiently than celecoxib in all the leukemic cell lines tested. Cell death was associated with downregulation of Mcl-1 protein expression. We also found that DMC induces endoplasmic reticulum stress, which is associated with a decreased of GRP78 protein expression and an alteration of cell cycle progression at the G1/S transition in U937 cells. Acco...Continue Reading

References

Jan 1, 1997·Progress in Cell Cycle Research·M Whitaker
Feb 22, 2002·Journal of Cellular Physiology·Yang Cao, Stephen M Prescott
Jun 26, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Verena JendrossekClaus Belka
Nov 5, 2003·Journal of Cellular and Molecular Medicine·Alexandrina Burlacu
Mar 17, 2004·Cancer Treatment Reviews·Juan Angel Fresno VaraManuel González-Barón
Sep 4, 2004·Genome Biology·N V Chandrasekharan, Daniel L Simmons
Apr 20, 2005·Oncogene·David Cobrinik
May 4, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Wanzhong WangJan-Erik Damber
Jun 23, 2005·Cancer Biology & Therapy·Paul DentSteven Grant
Aug 3, 2005·Circulation·Elliott M AntmanJoseph Loscalzo
Nov 1, 2005·The Journal of Thoracic and Cardiovascular Surgery·Leah M BackhusRoss M Bremner
Nov 30, 2005·The American Journal of Pathology·Paola SecchieroGiorgio Zauli
Dec 13, 2005·Nature Clinical Practice. Oncology·Pierre Fenaux
May 6, 2006·Molecular Pharmacology·James A McCubreyRichard A Franklin
Aug 19, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Shuhong ZhangSherif S Farag
Apr 3, 2008·Cancer Research·Seok-Hyun KimWafik S El-Deiry
Aug 14, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alain C MitaFrancis J Giles
Aug 30, 2008·Srpski arhiv za celokupno lekarstvo·Tatjana Stankovic, Eliot Marston
Dec 23, 2008·Cellular and Molecular Life Sciences : CMLS·C Akgul
Mar 12, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Robert MutterHak Choy
Apr 2, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Yuhui ShiJames J Pestka
Apr 11, 2009·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Tina X LeeLong-Sheng Chang
Jan 28, 2010·Neuropathology and Applied Neurobiology·J M A KuijlenW Helfrich
Mar 4, 2010·Molecular Cancer Therapeutics·Jenilyn J VirreyFlorence M Hofman
Mar 27, 2010·International Journal of Cell Biology·Cyril SobolewskiMarc Diederich
May 25, 2010·Biochemical and Biophysical Research Communications·Erik NorbergBoris Zhivotovsky
May 28, 2010·Journal of Cellular Biochemistry·Lu-Hua Zhang, Xiang Zhang
Jul 6, 2010·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Yidan LinLongqi Chen

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Citations

Oct 27, 2016·Journal of Cellular and Molecular Medicine·Bo ZhangNengming Lin
Dec 28, 2016·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Qi WuMingyao Yang
Dec 19, 2020·Pharmaceuticals·Diana Xochiquetzal Robledo-CadenaSara Rodríguez-Enríquez
Feb 8, 2020·Journal of Medicinal Chemistry·Lucie PeterkováSilvie Rimpelová
Jan 27, 2020·Cardiovascular Pathology : the Official Journal of the Society for Cardiovascular Pathology·Kiran A VaidyaJonathan T Butcher
Mar 5, 2019·Biochemical Pharmacology·Christian Bailly, Michael J Waring

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