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Journal of Healthcare Engineering
Volume 4 (2013), Issue 1, Pages 47-66
Research Article

Low Probability Activation of Bax/Bak Can Induce Selective Killing of Cancer Cells by Generating Heterogeneity in Apoptosis

Subhadip Raychaudhuri1 and Somkanya C. Das2,3

1Department of Chemistry, University of California, Davis, California, USA
2Genome Center, University of California, Davis, California, USA
3Department of Biomedical Engineering, University of California, Davis, California, USA

Received 1 July 2012; Accepted 1 November 2012

Copyright © 2013 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Biomimetic pro-apoptotic agents (e.g., BH3 mimetics) have been shown to activate the intrinsic death pathway (Type 2 apoptosis) selectively in cancer cells, a mechanism that can be key to developing successful anti-cancer therapy. This work reports mathematical modeling and computer simulations to explore the mechanisms for cancer cell apoptosis. The results indicate that a combination of low probability Bid-Bax type reaction along with overexpressed reactant molecules allows specific killing of cancer cells. Low-probability activation of Bax also emerges as a basis for inherent cell-to-cell variability in apoptotic activation. Variations in Bcl-2 to Bax ratio within a cancer cell population can further affect intrinsic fluctuations generated due to the stochastic Bid-Bax reaction. Such heterogeneity in apoptosis resistance can also provide a mechanism for the origin of cells with higher tumorigenic potential (cancer stem-like cells). The implications of our results for cancer therapy, such as in minimizing stochastic fluctuations in cancer cell death, are discussed.