Natural Computing

, Volume 10, Issue 3, pp 993–1015 | Cite as

A discrete Petri net model for cephalostatin-induced apoptosis in leukemic cells

  • Eva M. Rodriguez
  • Anita Rudy
  • Ricardo C. H. del Rosario
  • Angelika M. Vollmar
  • Eduardo R. Mendoza


Understanding the mechanisms involved in apoptosis has been an area of extensive study due to its critical role in the development and homeostasis of multi-cellular organisms. Our special interest lies in understanding the apoptosis of tumor cells which is mediated by novel potential drugs. Cephalostatin 1 is a marine compound that can induce apoptosis in leukemic cells in a dose- and time-dependent manner even at nano-molar concentrations using a recently discovered pathway that excludes the receptor-mediated pathway and which includes both the mitochondrial and endoplasmic reticulum pathways (Dirsch et al., Cancer Res 63:8869–8876, 2003; López-Antón et al., J Biol Chem 28:33078–33086, 2006). In this paper, the methods and tools of Petri net theory are used to construct, analyze, and validate a discrete Petri net model for cephalostatin 1-induced apoptosis. Based on experimental results and literature search, we constructed a discrete Petri net consisting of 43 places and 59 transitions. Standard Petri net analysis techniques such as structural and invariant analyses and a recently developed modularity analysis technique using maximal abstract dependent transition sets (ADT sets) were employed. Results of these analyses revealed model consistency with known biological behavior. The sub-modules represented by the ADT sets were compared with the functional modules of apoptosis identified by Alberghina and Colangelo (BMC Neurosci 7(Suppl 1):S2, 2006).


Apoptosis Cephalostatin 1 Discrete Petri net Invariant analysis Maximal abstract dependent transition sets (ADT sets) Modularity analysis Structural analysis 

Supplementary material

11047_2009_9153_MOESM1_ESM.doc (118 kb)
Supplementary material 1 (DOC 118 kb)


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Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Eva M. Rodriguez
    • 1
    • 3
  • Anita Rudy
    • 2
  • Ricardo C. H. del Rosario
    • 3
    • 4
  • Angelika M. Vollmar
    • 2
  • Eduardo R. Mendoza
    • 5
    • 6
  1. 1.Department of MathematicsUniversity of Asia and the PacificPasig CityPhilippines
  2. 2.Department of Pharmacy, Center for Drug ResearchLudwig-Maximilians UniversityMunichGermany
  3. 3.Institute of MathematicsUniversity of the Philippines DilimanQuezon CityPhilippines
  4. 4.Department of Membrane BiochemistryMax-Planck Institute of BiochemistryMunichGermany
  5. 5.Department of Computer ScienceUniversity of the Philippines DilimanQuezon CityPhilippines
  6. 6.Physics Department and Center for NanoScienceLudwig-Maximilians UniversityMunichGermany

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