title: Cellular automata modeling of FASL-initiated apoptosis.
abstract: Two strategies for fighting cancer by modulating FASL-induced apoptosis were modeled by 2D-cellular automata. Our models predict that cancer cells can be killed by maximizing the apoptosis via joint suppression of FLIP and IAP inhibitors by siRNA and SMAC proteins, respectively. It was also predicted that the presumed feedback loop CASP3-->CASP9-->|IAP in the intrinsic pathway accelerates the apoptosis, but does not change significantly the concentration of DFF40, the protein that decomposes DNA. The alternative strategy of preventing the killing of the immune system's T-cells, via minimizing their tumor-induced FAS-L apoptosis by overexpression of FLIP and IAP, was also shown to be promising with a predicted considerable synergy action of the two inhibitors. Dual suppression or overexpression of apoptosis inhibitors emerges thus as promising approach in the fight against cancer. Our modeling has also brought some light on the process of turning type-I cells into type-II ones, which emerges as compensatory mechanism in case of damaged or silenced FASL pathway by preserving about the same self-death level at only 10-12% lower performance rate.
authors.affiliation: Department of Chemical and Life Science Engineering, Virginia Commonwealth University, 601 West Main Street, P.O. Box 843068, Richmond, Virginia 23284-3068, USA.
authors.forename: Advait
authors.initials: A
authors.lastname: Apte
authors.forename: Danail
authors.initials: D
authors.lastname: Bonchev
authors.forename: Stephen
authors.initials: S
authors.lastname: Fong
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D053222:Fas Ligand Protein / Q000378:metabolism*; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D008954:Models, Biological; D009369:Neoplasms / Q000175:diagnosis; D009842:Oligopeptides / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D053222:Fas Ligand Protein; D053200:Fas-Associated Death Domain Protein; D051034:Inhibitor of Apoptosis Proteins; D009842:Oligopeptides; D034741:RNA, Small Interfering; C532637:SMAC peptide