Share This Article:

Kinetic Monte Carlo Study of the Type 1/Type 2 Choice in Apoptosis Elucidates Selective Killing of Cancer Cells under Death Ligand Induction

Full-Text HTML XML Download Download as PDF (Size:6221KB) PP. 22-39
DOI: 10.4236/ojapo.2015.41003    2,183 Downloads   2,634 Views   Citations

ABSTRACT

Death ligand mediated apoptotic activation is a mode of cell death that is widely used in cellular and physiological situations. Interest in studying death ligand induced apoptosis has increased due to the promising role of recombinant soluble forms of death ligands (mainly recombinant TRAIL) in anti-cancer therapy. A clear elucidation of how death ligands activate the type 1 and type 2 apoptotic pathways in healthy and cancer cells may help develop better chemotherapeutic strategies. In this work, we use kinetic Monte Carlo simulations to address the problem of type 1/ type 2 choice in death ligand mediated apoptosis of cancer cells. Our study provides insights into the activation of membrane proximal death module that results from complex interplay between death and decoy receptors. Relative abundance of death and decoy receptors was shown to be a key parameter for activation of the initiator caspases in the membrane module. Increased concentration of death ligands frequently increased the type 1 activation fraction in cancer cells, and, in certain cases changed the signaling phenotype from type 2 to type 1. Results of this study also indicate that inherent differences between cancer and healthy cells, such as in the membrane module, may allow robust activation of cancer cell apoptosis by death ligand induction. At the same time, large cell-to-cell variability through the type 2 pathway was shown to provide protection for healthy cells. Such elucidation of selective activation of apoptosis in cancer cells addresses a key question in cancer biology and cancer therapy.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Raychaudhuri, S. (2015) Kinetic Monte Carlo Study of the Type 1/Type 2 Choice in Apoptosis Elucidates Selective Killing of Cancer Cells under Death Ligand Induction. Open Journal of Apoptosis, 4, 22-39. doi: 10.4236/ojapo.2015.41003.

References

[1] Falschlehner, C., Emmerich, C.H., Gerlach, B. and Walczak, H. (2007) TRAIL Signalling: Decisions between Life and Death. The International Journal of Biochemistry & Cell Biology, 39, 1462-1475.
http://dx.doi.org/10.1016/j.biocel.2007.02.007
[2] Shirley, S., Morizot, A. and Micheau, O. (2011) Regulating TRAIL Receptor-Induced Cell Death at the Membrane: A Deadly Discussion. Recent Patents on Anti-Cancer Drug Discovery, 6, 311-323.
http://dx.doi.org/10.2174/157489211796957757
[3] Kurita, S., Mott, J.L., Cazanave, S.C., Fingas, C.D., Guicciardi, M.E., Bronk, S.F., et al. (2011) Hedgehog Inhibition Promotes a Switch from Type II to Type I Cell Death Receptor Signaling in Cancer Cells. PLoS ONE, 6, e18330. http://dx.doi.org/10.1371/journal.pone.0018330
[4] Picarda, G., Trichet, V., Teletchea, S., Heymann, D. and Redini, F. (2012) TRAIL Receptor Signaling and Therapeutic Option in Bone Tumors: The Trap of the Bone Microenvironment. American Journal of Cancer Research, 2, 45-64.
[5] Mérino, D., Lalaoui, N., Morizot, A., Schneider, P., Solary, E. and Micheau, O. (2006) Differential Inhibition of TRAIL-Mediated DR5-DISC Formation by Decoy Receptors 1 and 2. Molecular and Cellular Biology, 26, 7046-7055. http://dx.doi.org/10.1128/MCB.00520-06
[6] Rathmell, J.C. and Thompson, C.B. (2002) Pathways of Apoptosis in Lymphocyte Development, Homeostasis, and Disease. Cell, 109, S97-S107. http://dx.doi.org/10.1016/S0092-8674(02)00704-3
[7] Elmore, S. (2007) Apoptosis: A Review of Programmed Cell Death. Toxicologic Pathology, 35, 495-516. http://dx.doi.org/10.1080/01926230701320337
[8] Takeda, K., Hayakawa, Y., Symth, M.J., Kayagaki, N., Yamaguchi, N., Kakuta, S., et al. (2001) Involvement of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand in Surveillance of Tumor Metastasis by Liver Natural Killer Cells. Nature Medicine, 7, 94-100. http://dx.doi.org/10.1038/83416
[9] Quintana, E., Shackleton, M., Sabel, M.S., Fullen, D.R., Johnson, T.M. and Morrison, S.J. (2008) Efficient Tumour Formation by Single Human Melanoma Cells. Nature, 456, 593-598.
http://dx.doi.org/10.1038/nature07567
[10] Smyth, M.J., Takeda, K., Hayakawa, Y., Peschon, J.J., van den Brink, M.R.M. and Yagita, H. (2003) Nature’s TRAIL—On a Path to Cancer Immunotherapy. Immunity, 18, 1-6.
http://dx.doi.org/10.1016/S1074-7613(02)00502-2
[11] Di Carlo, M. (2010) Beta Amyloid Peptide: From Different Aggregation Forms to the Activation of Different Biochemical Pathways. European Biophysics Journal, 39, 877-888.
http://dx.doi.org/10.1007/s00249-009-0439-8
[12] Picone, P., Carrotta, R., Montana, G., Rita Nobile, M., San Biagio, P.L. and Di Carlo, M. (2009) Aβ Oligomers and Fibrillar Aggregates Induce Different Apoptotic Pathways in LAN5 Neuroblastoma Cell Cultures. Biophysical Journal, 96, 4200-4211. http://dx.doi.org/10.1016/j.bpj.2008.11.056
[13] Fossati, S., Ghiso, J. and Rostagno, A. (2012) TRAIL Death Receptors DR4 and DR5 Mediate Cerebral Microvascular Endothelial Cell Apoptosis Induced by Oligomeric Alzheimer’s Aβ. Cell Death and Disease, 3, e321. http://dx.doi.org/10.1038/cddis.2012.55
[14] Raychaudhuri, S. and Raychaudhuri, S.C. (2013) Monte Carlo Study Elucidates the Type 1/Type 2 Choice in Apoptotic Death Signaling in Healthy and Cancer Cells. Cells, 2, 361-392.
http://dx.doi.org/10.3390/cells2020361
[15] Raychaudhuri, S. and Raychaudhuri, S.C. (2014) Death Ligand Concentration and the Membrane Proximal Signaling Module Regulate the Type 1/Type 2 Choice in Apoptotic Death Signaling. Systems and Synthetic Biology, 8, 83-97. http://dx.doi.org/10.1007/s11693-013-9124-4
[16] Certo, M., Del Gaizo Moore, V., Nishino, M., Wei, G., Korsmeyer, S., Armstrong, S.A. and Letai, A. (2006) Mitochondria Primed by Death Signals Determine Cellular Addiction to Antiapoptotic BCL-2 Family Members. Cancer Cell, 9, 351-365. http://dx.doi.org/10.1016/j.ccr.2006.03.027
[17] Skommer, J., Brittain, T. and Raychaudhuri, S. (2010) Bcl-2 Inhibits Apoptosis by Increasing the Time-to-Death and Intrinsic Cell-to-Cell Variations in the Mitochondrial Pathway of Cell Death. Apoptosis, 15, 1223-1233. http://dx.doi.org/10.1007/s10495-010-0515-7
[18] Skommer, J., Das, S.C., Nair, A., Brittain, T. and Raychaudhuri, S. (2011) Nonlinear Regulation of Commitment to Apoptosis by Simultaneous Inhibition of Bcl-2 and XIAP in Leukemia and Lymphoma Cells. Apoptosis, 16, 619-626. http://dx.doi.org/10.1007/s10495-011-0593-1
[19] Raychaudhuri, S. and Das, S.C. (2013) Low Probability Activation of Bax/Bak Can Induce Selective Killing of Cancer Cells by Generating Heterogeneoity in Apoptosis. Journal of Healthcare Engineering, 4, 47-66. http://dx.doi.org/10.1260/2040-2295.4.1.47
[20] Breen, L., Heenan, M., Amberger-Murphy, V. and Clynes, M. (2007) Investigation of the Role of p53 in Chemotherapy Resistance of Lung Cancer Cell Lines. Anticancer Research, 27, 1361-1364.
[21] Lin, T.Y., Huang, X.F., Gu, J., Zhang, L.D., Roth, J.A., Xiong, M.M., et al. (2002) Long-Term Tumor-Free Survival from Treatment with the GFP-TRAIL Fusion Gene Expressed from the hTERT Promoter in Breast Cancer Cells. Oncogene, 21, 8020-8028. http://dx.doi.org/10.1038/sj.onc.1205926
[22] Pan, G., Ni, J., Wei, Y.F., Yu, G.L., Gentz, R. and Dixit, V.M. (1997) An Antagonist Decoy Receptor and a Death Domain-Containing Receptor for TRAIL. Science, 277, 815-818.
http://dx.doi.org/10.1126/science.277.5327.815
[23] Sheridan, J.P., Marsters, S.A., Pitti, R.M., Gurney, A., Skubatch, M., Baldwin, D., et al. (1997) Control of TRAIL-Induced Apoptosis by a Family of Signaling and Decoy Receptors. Science, 277, 818-821.
http://dx.doi.org/10.1126/science.277.5327.818
[24] Apoptosis in Health and Diseases (2010) First Paperback. Cambridge University Press, Cambridge, UK.
[25] Ngamkitidechakul, C., Jaijoy, K., Hansakul, P., Soonthornchareonnon, N. and Sireeratawong, S. (2010) Antitumour Effects of Phyllanthus emblica L.: Induction of Cancer Cell Apoptosis and Inhibition of in Vivo Tumour Promotion and in Vitro Invasion of Human Cancer Cells. Phytotherapy Research, 24, 1405-1413. http://dx.doi.org/10.1002/ptr.3127
[26] Guicciardi, M.E. and Gores, G.J. (2009) Life and Death by Death Receptors. The FASEB Journal: The Journal of the American Societies for Experimental Biology, 23, 1625-1637.
http://dx.doi.org/10.1096/fj.08-111005
[27] Hua, F., Cornejo, M.G., Cardone, M.H., Stokes, C.L. and Lauffenburger, D.A. (2005) Effects of Bcl-2 Levels on Fas Signaling-Induced Caspase-3 Activation: Molecular Genetic Tests of Computational Model Predictions. Journal of Immunology, 175, 985-995. http://dx.doi.org/10.4049/jimmunol.175.2.985
[28] Schneider, P., Bodmer, J.L., Thome, M., Hofmann, K., Holler, N. and Tschopp, J. (1997) Characterization of Two Receptors for TRAIL. FEBS Letters, 416, 329-334.
http://dx.doi.org/10.1016/S0014-5793(97)01231-3
[29] Meng, X.W., Peterson, K.L., Dai, H., Schneider, P., Lee, S.H., Zhang, J.S., et al. (2011) High Cell Surface Death Receptor Expression Determines Type I versus Type II Signaling. Journal of Biological Chemistry, 286, 35823-35833. http://dx.doi.org/10.1074/jbc.M111.240432
[30] Gu, C., Zhang, J.J., Chen, Y.Y. and Lei, J.Z. (2011) A Trigger Model of Apoptosis Induced by Tumor Necrosis Factor Signaling. BMC Systems Biology, 5, S13.
http://dx.doi.org/10.1186/1752-0509-5-S1-S13
[31] Sanlioglu, A.D., Dirice, E., Aydin, C., Erin, N., Koksoy, S. and Sanlioglu, S. (2005) Surface TRAIL Decoy Receptor-4 Expression Is Correlated with TRAIL Resistance in MCF7 Breast Cancer Cells. BMC Cancer, 5, 54. http://dx.doi.org/10.1186/1471-2407-5-54
[32] Fricker, N., Beaudouin, J., Richter, P., Eils, R., Krammer, P.H. and Lavrik, I.N. (2010) Model-Based Dissection of CD95 Signaling Dynamics Reveals both a Pro- and Antiapoptotic Role of c-FLIPL. Journal of Cell Biology, 190, 377- 389. http://dx.doi.org/10.1083/jcb.201002060
[33] Raychaudhuri, S., Willgohs, E., Nguyen, T.N., Khan, E.M. and Goldkorn, T. (2008) Monte Carlo Simulation of Cell Death Signaling Predicts Large Cell-to-Cell Stochastic Fluctuations through the Type 2 Pathway of Apoptosis. Biophysical Journal, 95, 3559-3562. http://dx.doi.org/10.1529/biophysj.108.135483
[34] Bagci, E.Z., Vodovotz, Y., Billiar, T.R., Ermentrout, G.B. and Bahar, I. (2006) Bistability in Apoptosis: Roles of Bax, Bcl-2, and Mitochondrial Permeability Transition Pores. Biophysical Journal, 90, 1546-1559.
http://dx.doi.org/10.1529/biophysj.105.068122
[35] Newman, M.E.J. and Barkema, G.T. (1999) Monte Carlo Methods in Statistical Physics. Oxford University Press, New York.
[36] Notta, F., Mullighan, C.G., Wang, J.C.Y., Poeppl, A., Doulatov, S., Phillips, L.A., et al. (2011) Evolution of Human BCR-ABL1 Lymphoblastic Leukaemia-Initiating Cells. Nature, 469, 362-367.
http://dx.doi.org/10.1038/nature09733
[37] Anderson, K., Lutz, C., van Delft, F.W., Bateman, C.M., Guo, Y.P., Colman, S.M., et al. (2011) Genetic Variegation of Clonal Architecture and Propagating Cells in Leukaemia. Nature, 469, 356-361.
http://dx.doi.org/10.1038/nature09650
[38] Hassan, M., Watari, H., AbuAlmaaty, A., Ohba, Y. and Sakuragi, N. (2014) Apoptosis and Molecular Targeting Therapy in Cancer. BioMed Research International, 2014, Article ID: 150845.
http://dx.doi.org/10.1155/2014/150845
[39] Sun, X.M., Bratton, S.B., Butterworth, M., MacFarlane, M. and Cohen, G.M. (2002) Bcl-2 and Bcl-xL Inhibit CD95- Mediated Apoptosis by Preventing Mitochondrial Release of Smac/DIABLO and Subsequent Inactivation of X-Linked Inhibitor-of-Apoptosis Protein. Journal of Biological Chemistry, 277, 11345-11351. http://dx.doi.org/10.1074/jbc.M109893200
[40] Maas, C., Verbrugge, I., de Vries, E., Savich, G., van de Kooij, L.W., Tait, S.W.G. and Borst, J. (2010) Smac/DIABLO Release from Mitochondria and XIAP Inhibition Are Essential to Limit Clonogenicity of Type I Tumor Cells after TRAIL Receptor Stimulation. Cell Death and Differentiation, 17, 1613-1623.
http://dx.doi.org/10.1038/cdd.2010.39
[41] Ho, I.A., Ng, W.H. and Lam, P.Y. (2010) FasL and FADD Delivery by a Glioma-Specific and Cell Cycle-Dependent HSV-1 Amplicon Virus Enhanced Apoptosis in Primary Human Brain Tumors. Molecular Cancer, 9, 270. http://dx.doi.org/10.1186/1476-4598-9-270
[42] Siegelin, M.D., Gaiser, T. and Siegelin, Y. (2009) The XIAP Inhibitor Embelin Enhances TRAIL-Mediated Apoptosis in Malignant Glioma Cells by Down-Regulation of the Short Isoform of FLIP. Neurochemistry International, 55, 423- 430. http://dx.doi.org/10.1016/j.neuint.2009.04.011
[43] Liu, X.G., Yue, P., Zhou, Z.M., Khuri, F.R. and Sun, S.-Y. (2004) Death Receptor Regulation and Celecoxib-Induced Apoptosis in Human Lung Cancer Cells. Journal of the National Cancer Institute, 96, 1769-1780. http://dx.doi.org/10.1093/jnci/djh322
[44] Yoshida, T., Konishi, M., Horinaka, M., Yasuda, T., Goda, A.E., Taniguchi, H., et al. (2008) Kaempferol Sensitizes Colon Cancer Cells to TRAIL-Induced Apoptosis. Biochemical and Biophysical Research Communications, 375, 129- 133. http://dx.doi.org/10.1016/j.bbrc.2008.07.131
[45] Johnson, C.E., Huang, Y.Y., Parrish, A.B., Smith, M.I., Vaughn, A.E., Zhang, Q., et al. (2007) Differential Apaf-1 Levels Allow Cytochrome c to Induce Apoptosis in Brain Tumors but Not in Normal Neural Tissues. Proceedings of the National Academy of Sciences of the United States of America, 104, 20820-20825. http://dx.doi.org/10.1073/pnas.0709101105
[46] Hu, R., Zhu, K., Li, Y.C., Yao, K., Zhang, R., Wang, H.H., Yang, W. and Liu, Z.G. (2011) Embelin Induces Apoptosis through Down-Regulation of XIAP in Human Leukemia Cells. Medical Oncology, 28, 1584-1588. http://dx.doi.org/10.1007/s12032-010-9601-5
[47] Marconi, M., Ascione, B., Ciarlo, L., Vona, R., Garofalo, T., Sorice, M., et al. (2013) Constitutive Localization of DR4 in Lipid Rafts Is Mandatory for TRAIL-Induced Apoptosis in B-Cell Hematologic Malignancies. Cell Death and Disease, 4, e863. http://dx.doi.org/10.1038/cddis.2013.389
[48] Yang, Y., Swennenhuis, J.F., Rho, H.S., Le Gac, S. and Terstappen, L.W. (2014) Parallel Single Cancer Cell Whole Genome Amplification Using Button-Valve Assisted Mixing in Nanoliter Chambers. PLoS ONE, 9, e107958. http://dx.doi.org/10.1371/journal.pone.0107958

  
comments powered by Disqus

Copyright © 2018 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.