文档介绍：Review article
Cellular stress response and apoptosis in cancer therapy
Ingrid Herr and Klaus-Michael Debatin
Anticancer treatment using cytotoxic drugs release apoptogenic factors (cytochrome c, way have a profound influence on apopto-
is considered to mediate cell death by acti- Apaf-1, AIF), leading to the activation of sis. Understanding plex interaction
vating key elements of the apoptosis pro- caspase-9. The stressed endoplasmic reticu- between different cellular programs pro-
gram and the cellular stress response. While lum (ER) contributes to apoptosis by the vides insights into sensitivity or resistance
proteolytic enzymes (caspases) serve as unfolded protein response pathway, which of tumor cells and identifies molecular tar-
main effectors of apoptosis, the mecha- induces ER chaperones, and by the ER gets for rational therapeutic intervention
nisms involved in activation of the caspase overload response pathway, which pro- strategies. (Blood. 2001;98:2603-2614)
system are less clear. Two distinct pathways duces cytokines via nuclear factor-B. Mul-
upstream of the caspase cascade have been tiple other stress-inducible molecules, such
identified. Death receptors, eg, CD95 (APO- as p53, JNK, AP-1, NF-B, PKC/MAPK/ERK,
1/Fas), trigger caspase-8, and mitochondria and members of the sphingomyelin path- © 2001 by The American Society of Hematology
Introduction
In an overall scenario, the development of malignant tumors results mediate cytokine processing. Caspases are cysteine proteases
from deregulated proliferation or an inability of cells to undergo produced as inactive zymogens that cleave their substrates at
apoptotic cell ,2 Anticancer drugs inhibit proliferation and aspartic acid residues contained within a tetrapeptide recognition
induce apoptosis in sensitive tumor ,4 The cellular targets for motif. Activation of initiator caspases (procaspase-8, -9, -10) leads
different cytotoxic agents are diverse. Thus, anticancer drugs