Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1389183 (autodigestion)
 317 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Programmed cell death (apoptosis) is an intrinsic part of organismal development and aging. Here we report that many nonsteroidal antiinflammatory drugs (NSAIDs) cause apoptosis when applied to v-src-transformed chicken embryo fibroblasts (CEFs). Cell death was characterized by morphological changes, the induction of tissue transglutaminase, and autodigestion of DNA. Dexamethasone, a repressor of cyclooxygenase (COX) 2, neither induced apoptosis nor altered the NSAID effect. Prostaglandin E2, the primary eicosanoid made by CEFs, also failed to inhibit apoptosis. Expression of the protooncogene bcl-2 is very low in CEFs and is not altered by NSAID treatment. In contrast, p20, a protein that may protect against apoptosis when fibroblasts enter G0 phase, was strongly repressed. The NSAID concentrations used here transiently inhibit COXs. Nevertheless, COX-1 and COX-2 mRNAs and COX-2 protein were induced. In some cell types, then, chronic NSAID treatment may lead to increased, rather than decreased, COX activity and, thus, exacerbate prostaglandin-mediated inflammatory effects. The COX-2 transcript is a partially spliced and nonfunctional form previously described. Thus, these findings suggest that COXs and their products play key roles in preventing apoptosis in CEFs and perhaps other cell types.
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PMID:Nonsteroidal antiinflammatory drugs cause apoptosis and induce cyclooxygenases in chicken embryo fibroblasts. 764 21

In essentially all tissues that have self-renewal capacity, there exists a delicate balance between cell production by mitogenesis and cell loss due to programmed cell death (PCD), which maintains total cell numbers within physiologically appropriate ranges. Genetic alterations that either dysregulate the cell division process, resulting in faster cell proliferation, or that affect physiological cell death mechanisms that cause slower rates of cell loss, occur frequently in human tumor cells and contribute to the clonal expansion of cancer cells in vivo. PCD is an active form of cell suicide that sometimes requires new gene expression for its initiation and that in many, but not all, cases culminates in a characteristic set of biochemical and morphological events. These include genomic DNA cleavage by endonucleases, chromatin condensation (pyknosis), nuclear fragmentation, proteolysis of cytoskeletal and other proteins, plasma membrane blebbing, and cell shrinkage. In many ways, these biochemical events can be viewed as a form of cellular autodigestion in which the macromolecular components of cells are degraded so that their constituent subunits can be recycled in the body. When present in their classical form, the morphological events accompanying this type of cell death are broadly termed apoptosis. Though well known for its role in the normal physiological cell death mechanisms that maintain tissue homeostasis, a wide variety of pathological conditions and external factors can trigger the PCD pathway. Included among these apoptotic stimuli are essentially all chemotherapeutic drugs and radiation, a finding of considerable relevance to our understanding of how currently available treatments of cancer work and for devising strategies for improving them. In this review, the regulation of PCD by members of the bcl-2 family of proteins is discussed, primarily within the context of human cancers where abnormalities in the expression of BCL2 family genes frequently occur and contribute both to the origins of cancer and our difficulty in treating it.
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PMID:Regulation of apoptosis by bcl-2 family proteins and its role in cancer and chemoresistance. 854 3