Targeting the Bcl-2 family of proteins in Hodgkin lymphoma

In vitro cytotoxicity, target modulation and drug combination studies of the Bcl-2 homology 3 mimetic ABT-737

Aarthi Jayanthan, Scott Howard, Tanya Trippett, Terzah Horton, James A. Whitlock, Lara Daisley, Victor Lewis, Aru Narendran

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

With currently available treatment, patients with refractory Hodgkin lymphoma (HL) or those who relapse multiple times have an extremely poor prognosis. Therefore, new agents and novel therapeutic approaches are urgently needed. Anti-apoptotic proteins such as Bcl-2 and Bcl-x have been associated with the growth and survival of Hodgkin Reed-Sternberg cells and are potential therapeutic targets. ABT-737 is a small molecule that inhibits the Bcl-2 family of apoptosis regulators. In this study, we show the concentration-dependent and time-dependent cytotoxicity of ABT-737 against cell lines derived from patients with HL. A concurrent reduction in a number of intracellular cell growth and survival related molecules, such as Bcl-2, Bcl-xl, NF-κB and survivin was also seen. Drug combination studies using a panel of conventional and novel therapeutic agents show that ABT-737 potentiates the activity of agents that have inherent anti-lymphoma activity and provide support for the evaluation of ABT-737 in the clinical setting.

Original languageEnglish (US)
Pages (from-to)1174-1182
Number of pages9
JournalLeukemia and Lymphoma
Volume50
Issue number7
DOIs
StatePublished - Aug 17 2009

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Drug Combinations
Hodgkin Disease
Proteins
Reed-Sternberg Cells
Apoptosis Regulatory Proteins
Therapeutics
Lymphoma
Cell Survival
Apoptosis
Recurrence
Cell Line
Survival
In Vitro Techniques
ABT-737
Growth

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Targeting the Bcl-2 family of proteins in Hodgkin lymphoma : In vitro cytotoxicity, target modulation and drug combination studies of the Bcl-2 homology 3 mimetic ABT-737. / Jayanthan, Aarthi; Howard, Scott; Trippett, Tanya; Horton, Terzah; Whitlock, James A.; Daisley, Lara; Lewis, Victor; Narendran, Aru.

In: Leukemia and Lymphoma, Vol. 50, No. 7, 17.08.2009, p. 1174-1182.

Research output: Contribution to journalArticle

Jayanthan, Aarthi ; Howard, Scott ; Trippett, Tanya ; Horton, Terzah ; Whitlock, James A. ; Daisley, Lara ; Lewis, Victor ; Narendran, Aru. / Targeting the Bcl-2 family of proteins in Hodgkin lymphoma : In vitro cytotoxicity, target modulation and drug combination studies of the Bcl-2 homology 3 mimetic ABT-737. In: Leukemia and Lymphoma. 2009 ; Vol. 50, No. 7. pp. 1174-1182.
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