• Corpus ID: 14226012

Low probability Bid-Bax reaction generates heterogeneity in apoptosis resistance of cancer and cancer stem cells

@article{Raychaudhuri2011LowPB,
  title={Low probability Bid-Bax reaction generates heterogeneity in apoptosis resistance of cancer and cancer stem cells},
  author={Subhadip Raychaudhuri},
  journal={arXiv: Molecular Networks},
  year={2011}
}
Variability in the tumorigenic potential among cancer cells within a tumor population is an unresolved fundamental issue in cancer biology. It is important to know whether cancer cells with higher tumorigenic potential, such as cancer stem cells, are only a small subpopulation. We attempt to address the question of variability in tumorigenic potential based on the heterogeneity in apoptosis resistance of cancer cells. We use stochastic differential equations and kinetic Monte Carlo simulations… 

References

SHOWING 1-10 OF 38 REFERENCES

How can we kill cancer cells: Insights from the computational models of apoptosis.

TLDR
Monte Carlo simulations of apoptotic signaling provides unexpected insights into the mechanisms of fractional cell killing induced by apoptosis-inducing agents, showing that not only variation in protein levels, but also inherent stochastic variability in signaling reactions, can lead to survival of a fraction of treated cancer cells.

Bcl-2 inhibits apoptosis by increasing the time-to-death and intrinsic cell-to-cell variations in the mitochondrial pathway of cell death

TLDR
It is suggested that intrinsic cell-to-cell stochastic variability in apoptotic signaling is sufficient to cause fractional killing of cancer cells after exposure to BH3 mimetics, an unanticipated facet of cancer chemoresistance.

Nonlinear regulation of commitment to apoptosis by simultaneous inhibition of Bcl-2 and XIAP in leukemia and lymphoma cells

TLDR
Using the computational probabilistic model of the apoptotic pathway, verified by experimental results from human leukemia and lymphoma cell lines, it is shown that inhibition of XIAP has a non-linear effect on sensitization towards apoptosis induced by the BH3 mimetic HA14-1.

Targeting the Bcl-2-regulated apoptosis pathway by BH3 mimetics: a breakthrough in anticancer therapy?

TLDR
This review will touch on the latest findings on BH3-only protein function and attempts to define the molecular properties of the so-called ‘BH3 mimetics,’ a novel class of anticancer agents, able to prompt apoptosis in tumor cells, regardless of their p53 or Bcl-2 status.

Mimicking the BH3 domain to kill cancer cells

TLDR
The BH3 mimetics are a new class of cancer drugs that specifically target a mechanism of cancer cell survival to selectively kill cancer cells.

Structure-based discovery of an organic compound that binds Bcl-2 protein and induces apoptosis of tumor cells.

  • J. L. WangD. Liu Z. Huang
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 2000
TLDR
The discovery of HA14-1, a small molecule and nonpeptidic ligand of a Bcl-2 surface pocket, provides a chemical probe to study B cl-2-regulated apoptotic pathways in vivo and could lead to the development of new therapeutic agents.

The small organic compound HA14-1 prevents Bcl-2 interaction with Bax to sensitize malignant glioma cells to induction of cell death.

TLDR
It is shown that ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy- 2-oxoethyl)-4H-chromene-3-carboxylate (HA14-1), a small organic compound recently proposed to function as an inhibitor of Bcl-2, increases the sensitivity of human glioblastoma cells to radiotherapy and chemotherapy.

Acute Myeloid Leukemia Stem Cells

  • J. Dick
  • Medicine
    Annals of the New York Academy of Sciences
  • 2005
TLDR
Recent clonal‐tracking studies showed that the LSC compartment is composed of different classes of LSCs, which can be distinguished on the basis of self‐renewal potential, which have important implications for the understanding of the leukemogenic process as well as the design of more effective therapies to eliminate AML based on eradication of the L SCs.