Histone deacetylase inhibitors specifically kill nonproliferating tumour cells

Oncogene
Andrew BurgessBrian Gabrielli

Abstract

Conventional chemotherapeutic drugs target proliferating cells, relying on often small differences in drug sensitivity of tumour cells compared to normal tissue to deliver a therapeutic benefit. Consequently, they have significant limiting toxicities and greatly reduced efficacy against nonproliferating compared to rapidly proliferating tumour cells. This lack of selectivity and inability to kill nonproliferating cells that exist in tumours with a low mitotic index are major failings of these drugs. A relatively new class of anticancer drugs, the histone deacetylase inhibitors (HDI), are selectively cytotoxic, killing tumour and immortalized cells but normal tissue appears resistant. Treatment of tumour cells with these drugs causes both G1 phase cell cycle arrest correlated with increase p21 expression, and cell death, but even the G1 arrested cells died although the onset of death was delayed. We have extended these observations using cells that were stably arrested by either serum starvation or expression of the cyclin-dependent kinase inhibitor p16(ink4a). We report that histone deacetylase inhibitors have similar cytotoxicity towards both proliferating and arrested tumour and immortalized cells, although the onset of apopt...Continue Reading

References

Jun 17, 1998·Proceedings of the National Academy of Sciences of the United States of America·S Y ArcherR A Hodin
Aug 24, 2000·Proceedings of the National Academy of Sciences of the United States of America·V M RichonP A Marks
Oct 24, 2001·Current Opinion in Oncology·P A MarksR A Rifkind
Jan 18, 2003·Blood·Nicholas MitsiadesKenneth C Anderson
Jun 26, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Robyn WarrenerBrian Gabrielli

❮ Previous
Next ❯

Citations

Apr 10, 2008·Cancer Chemotherapy and Pharmacology·Rafael B ErlichAlexander Guminski
Dec 4, 2010·Investigational New Drugs·Sridurga MithraprabhuAndrew Spencer
Dec 17, 2010·Investigational New Drugs·Michael DickinsonH Miles Prince
Apr 29, 2010·Current Hematologic Malignancy Reports·Mhairi Copland
Nov 10, 2009·Medical Oncology·Z StojsicI Boricic
Dec 20, 2008·Cell Death and Differentiation·G-H HaC-W Lee
Oct 26, 2011·Immunology and Cell Biology·Matthew J SweetDavid P Fairlie
Nov 9, 2011·Immunology and Cell Biology·Graham R Leggatt, Brian Gabrielli
Sep 11, 2007·Oncogene·F E StevensB Gabrielli
Jan 12, 2010·Human Reproduction Update·Marleen M H J van GelderNel Roeleveld
Sep 27, 2013·Journal of Molecular Cell Biology·Simona CitroSusanna Chiocca
May 20, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ling Li, Ravi Bhatia
Aug 4, 2012·Future Medicinal Chemistry·Giuseppe GianniniManuela Rodriquez
Nov 26, 2005·Expert Opinion on Investigational Drugs·Paul A Marks, Milos Dokmanovic
Aug 7, 2010·Expert Opinion on Investigational Drugs·Paul A Marks
Apr 5, 2014·Thérapie·Marleen M H J van GelderNel Roeleveld
Aug 24, 2013·Critical Reviews in Oncology/hematology·Kendra L SweetJavier Pinilla-Ibarz
Aug 22, 2012·Cancer Letters·Leslie A Crews, Catriona H M Jamieson
Jun 26, 2009·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Valérie LobjoisAnnie Valette
May 17, 2005·Pigment Cell Research·Glen M BoylePeter G Parsons
May 22, 2009·Journal of Cellular Biochemistry·P A Marks, W-S Xu
Sep 19, 2008·Cancer·Grace K Dy, Alex A Adjei
Apr 25, 2007·International Journal of Cancer. Journal International Du Cancer·Thomas BeckersKarl Sanders
Sep 18, 2008·International Journal of Cancer. Journal International Du Cancer·Mari BjörkmanOlli P Kallioniemi
Mar 23, 2013·British Journal of Pharmacology·A SinclairT L Holyoake
Oct 8, 2005·Seminars in Oncology·David S Schrump, Dao M Nguyen
Dec 30, 2014·Cancer·James R Whittle, Jayesh Desai

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Related Papers

Nature Reviews. Drug Discovery
Jessica E BoldenRicky Johnstone
Proceedings of the National Academy of Sciences of the United States of America
J S UngerstedtP A Marks
Journal of Neuroscience Research
Vishnu KannanHendrikus W G M Boddeke
© 2022 Meta ULC. All rights reserved