Caspase-3-mediated spontaneous death in neutrophils is a prototype of programmed cell death and is critical for modulating physiopathological inflammatory responses; however, the underlying regulatory pathways remain ill defined. Here we determined that in aging neutrophils, the cleavage and activation of caspase-3 is independent of the canonical caspase-8- or caspase-9-mediated pathway. Instea...

This issue of Methods contains a series of articles that cover the major techniques used to measure apoptosis, necrosis and variations thereof, at the population, single cell, organelle and molecular level. Although we used to think of apoptosis as programmed or regulated cell death and necrosis as strictly non-programmed or unregulated cell death [1,2], data have emerged in recent years which ...

Mutations in the gene ced-3, which encodes a protease similar to interleukin-1beta converting enzyme and related proteins termed caspases, prevent programmed cell death in the nematode Caenorhabditis elegans. We used site-directed mutagenesis to demonstrate that both the presumptive active-site cysteine of the CED-3 protease and the aspartate residues at sites of processing of the CED-3 proprot...

Studies in Drosophila have provided a detailed understanding of how programmed cell death is regulated by steroid hormones during development. This work has defined a two-step hormone-triggered regulatory cascade that results in the coordinate induction of central players in the death pathway, including the reaper and hid death activators, the Apaf-1 ortholog dark, and the dronc apical caspase ...

Programmed cell death (PCD) had been widely used synonymously to caspase-mediated apoptosis until caspase-independent cell death was described. Identification of necrosis as a regulated process in ischaemic conditions has recently changed our understanding of PCD. At least three pathways of programmed necrosis (PN) have been identified. First, receptor-interacting protein kinase 3 (RIP3)-depend...

Genetic analysis of programmed cell death in Drosophila reveals many similarities with mammals. Heretofore, a missing link in the fly has been the absence of any Bcl-2/Bax family members, proteins that function in mammals as regulators of mitochondrial cytochrome c release. A Drosophila homologue of the human killer protein Bok (DBok) was identified. The predicted structure of DBok is similar t...

the purpose of the present study is to investigate the cytotoxicity/apoptotic effect of 2-chloro-2′-deoxyadenosine, cladribine, (2-cda) in the human breast cancer cell line, mda-mb468 (estrogen receptor negative, er−). mtt [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2h tetrazolium bromide] assay, annexin v-fluorescein/pi and hoechst 33258 staining were used to detect cytotoxicity and cell apopto...

Apoptotic death evasion is a hallmark of cancer progression. In this context, past decades have witnessed cytotoxic agents targeting apoptosis. However, owing to cellular defects in the apoptotic machinery, tumors develop resistance apoptosis-based therapies. Hence, nonapoptotic cell-death pathways displays enhanced therapeutic success apoptosis-defective tumor cells. Exploitation multifunction...