alexa Nonlinear regulation of commitment to apoptosis by simultaneous inhibition of Bcl-2 and XIAP in leukemia and lymphoma cells.
Bioinformatics & Systems Biology

Bioinformatics & Systems Biology

Journal of Computer Science & Systems Biology

Author(s): Skommer J, Das SC, Nair A, Brittain T, Raychaudhuri S

Abstract Share this page

Abstract Apoptosis is a complex pathway regulated by the concerted action of multiple pro- and anti-apoptotic molecules. The intrinsic (mitochondrial) pathway of apoptosis is governed up-stream of mitochondria, by the family of Bcl-2 proteins, and down-stream of mitochondria, by low-probability events, such as apoptosome formation, and by feedback circuits involving caspases and inhibitor of apoptosis proteins (IAPs), such as XIAP. All these regulatory mechanisms ensure that cells only commit to death once a threshold of damage has been reached and the anti-apoptotic reserve of the cell is overcome. As cancer cells are invariably exposed to strong intracellular and extracellular stress stimuli, they are particularly reliant on the expression of anti-apoptotic proteins. Hence, many cancer cells undergo apoptosis when exposed to agents that inhibit anti-apoptotic Bcl-2 molecules, such as BH3 mimetics, while normal cells remain relatively insensitive to single agent treatments with the same class of molecules. Targeting different proteins within the apoptotic network with combinatorial treatment approaches often achieves even greater specificity. This led us to investigate the sensitivity of leukemia and lymphoma cells to a pro-apoptotic action of a BH3 mimetic combined with a small molecule inhibitor of XIAP. Using the computational probabilistic model of the apoptotic pathway, verified by experimental results from human leukemia and lymphoma cell lines, we show that inhibition of XIAP has a non-linear effect on sensitization towards apoptosis induced by the BH3 mimetic HA14-1. This study justifies further ex vivo and animal studies on the potential of the treatment of leukemia and lymphoma with a combination of BH3 mimetics and XIAP inhibitors. This article was published in Apoptosis and referenced in Journal of Computer Science & Systems Biology

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Relevant Topics

Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri, Food, Aqua and Veterinary Science Journals

Dr. Krish

1-702-714-7001 Extn: 9040

Clinical and Biochemistry Journals

Datta A

1-702-714-7001Extn: 9037

Business & Management Journals


1-702-714-7001Extn: 9042

Chemical Engineering and Chemistry Journals

Gabriel Shaw

1-702-714-7001 Extn: 9040

Earth & Environmental Sciences

Katie Wilson

1-702-714-7001Extn: 9042

Engineering Journals

James Franklin

1-702-714-7001Extn: 9042

General Science and Health care Journals

Andrea Jason

1-702-714-7001Extn: 9043

Genetics and Molecular Biology Journals

Anna Melissa

1-702-714-7001 Extn: 9006

Immunology & Microbiology Journals

David Gorantl

1-702-714-7001Extn: 9014

Informatics Journals

Stephanie Skinner

1-702-714-7001Extn: 9039

Material Sciences Journals

Rachle Green

1-702-714-7001Extn: 9039

Mathematics and Physics Journals

Jim Willison

1-702-714-7001 Extn: 9042

Medical Journals

Nimmi Anna

1-702-714-7001 Extn: 9038

Neuroscience & Psychology Journals

Nathan T

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

John Behannon

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

1-702-714-7001 Extn: 9042

© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version