Classification of cell death: recommendations of the Nomenclature Committee on Cell Death

Kroemer, Guido; El‐Deiry, Wafik S.; Golstein, Pierre; Marynen, Peter; Vaux, David L.; Vandenabeele, Peter; Zhivotovsky, Boris; Blagosklonny, Mikhail V.; Malorni, Walter; Knight, Richard; Piacentini, Mauro; Nagata, Shinji; Melino, Gerry

doi:10.1038/sj.cdd.4401724

Cited by 1,226 publications

(1,439 citation statements)

References 24 publications

Supporting

Mentioning

1,305

Contrasting

Unclassified

108

Order By: Relevance

“…However, mitotic cells were occasionally seen among the cells treated with P-GG-DOX. These findings indicate a high diversity of cellular responses for a given drug treatment and this variability should always be considered when characterizing the mode of cell death [23].…”

Section: Resultsmentioning

confidence: 93%

Liberation of doxorubicin from HPMA copolymer conjugate is essential for the induction of cell cycle arrest and nuclear fragmentation in ovarian carcinoma cells

Malugin

Kopečková

Kopeček

2007

Journal of Controlled Release

View full text Add to dashboard Cite

Despite intensive study, the molecular mechanism for cell toxicity of N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-bound doxorubicin remains unclear. Moreover, the ability of the released drug to accumulate in the nucleus has also been questioned. We have hypothesized that the pattern of cell cycle progression is a useful indicator for the presence of free doxorubicin in the nucleus and its interaction with nuclear DNA. The effects of HPMA copolymer-bound doxorubicin on cell cycle progression were evaluated in this study in cultured human ovarian cancer A2780 cells. We determined that P-GFLG-DOX, but not P-GG-DOX, initiates cell cycle arrest and nuclear fragmentation in the same manner as free DOX, but with a time-delay. Our data indicate that drug release from the conjugate is required for the apoptotic activity associated with the conjugate.

show abstract

Section: Resultsmentioning

confidence: 93%

Liberation of doxorubicin from HPMA copolymer conjugate is essential for the induction of cell cycle arrest and nuclear fragmentation in ovarian carcinoma cells

Malugin

Kopečková

Kopeček

2007

Journal of Controlled Release

View full text Add to dashboard Cite

show abstract

“…2,3,[18][19][20] The role of drug-induced autophagy, however, is poorly understood, and given the protective role of autophagy in times of cellular starvation, it remains unclear whether the drug-induced autophagy noted following exposure of cells to agents such as TMZ is protective from, or contributory to, cell death. 3,8 In this study, we show that autophagy induced by two distinct DNA damaging agents clearly protects several GBM cell lines from cell death preceded by multimicronucleation.…”

Section: Discussionmentioning

confidence: 99%

“…The cells that were large (absent of cytoplasmic shrinkage) and contained separate micronuclei with evenly stained chromatin (absence of chromatin condensation) were defined as multinucleated cells as reported previously. 19,25,26 The percentage of multimicronucleated cells was determined after scoring more than 100 nuclei for each experiment. Each experiment was repeated at least three times.…”

Section: Discussionmentioning

confidence: 99%

DNA damaging agent-induced autophagy produces a cytoprotective adenosine triphosphate surge in malignant glioma cells

et al. 2006

View full text Add to dashboard Cite

Although autophagy enhances cell survival in nutrient-deprived cells by increasing adenosine triphosphate (ATP) production, it remains unclear if autophagy functions similarly in cells treated with cytotoxic chemotherapy agents. To address this issue, we measured both the ability of DNA damaging agents (Temozolomide, and Etoposide) to induce an autophagy-dependent production of ATP, and the effects of modulation of autophagy on drug-induced cell death. Both drugs induced an autophagyassociated increase in ATP production in multiple glioma cell lines. The drug-induced ATP surge could not be blocked by glucose starvation, but could be blocked by preincubation with the autophagy inhibitor 3-methyladenine (3-MA), an siRNA targeting beclin 1, or the mitochondrial inhibitor oligomycin. Inhibition of autophagy-induced ATP production increased nonapoptotic cell death associated with micronucleation, while restoration of the 3-MA-inhibited ATP surge by addition of pyruvate suppressed cell death. These results show that DNA damaging agents induce an autophagy-associated ATP surge that protects cells and may contribute to drug resistance. Autophagy is a process by which subcellular constituents are degraded in autophagosomes/autolysosomes in response to stress. 1 Whereas growth factors enhance the ability of metazoan cells to take up extracelluar nutrients and suppress autophagy, deprivation of either growth factors or extracellular nutrients leads to decreased nutrient uptake and derepression of autophagy. The catabolic autophagy process is believed to allow starving cells to support adenosine triphosphate (ATP) production and avoid cell death. 2,3 The autophagic process is regulated by both class I and class III phosphatidylinositol 3-kinase (PI3K) pathways. 2,4,5 Mammalian target of Rapamycin (mTOR) functions downstream of the class-I PI3K/Akt, and is a key negative regulator of autophagy. In this role, mTOR serves as a metabolic sensor that coordinates crosstalk between nutrient availability and autophagy. 6,7 In contrast, class III PI3K positively regulates autophagy. The formation of a preautophagosomal isolation membrane that encloses cytoplasmic cargo is positively regulated by phosphatidylinositol 3-phosphate, the products of class III PI3K phosphorylation. 4 It has also been suggested that the trafficking of autophagosomes is regulated by class III PI3Ks, 4,5 an idea supported by the observation that 3-methyladenine (3-MA), which inhibits class III PI3K activity, also inhibits autophagosome formation and is widely used as an autophagy inhibitor. 5 It is also known that autophagy is induced in cancer cells derived from tissues such as breast, colon, prostate and brain in response to a variety of anticancer therapies. 3,8 However, autophagy in response to these drugs can produce different outcomes, in some cases promoting cell adaptation and survival similar to what is seen in nutrient deprived cells, while in other cases, inducing programmed cell death type. The role of drug-induced autophagy in cell death or surv...

show abstract

“…chromatin condensation, and karyorhexis, i.e. nuclear fragmentation), the plasma membrane (phosphatidylserine exposure) and, more generally, the entire cell that progressively shrinks and eventually breaks into several "apoptotic bodies" [3,4]. Apoptosis may be separated into at least three distinct phases: initiation, integration/decision and execution/degradation.…”

Section: Intrinsic and Extrinsic Apoptosis Pathwaysmentioning

confidence: 99%

Methods for the assessment of mitochondrial membrane permeabilization in apoptosis

et al. 2007

View full text Add to dashboard Cite

Mitochondrial membrane permeabilization (MMP) is considered as the "point-of-no-return" in numerous models of programmed cell death. Indeed, mitochondria determine the intrinsic pathway of apoptosis, and play a major role in the extrinsic route as well. MMP affects the inner and outer mitochondrial membranes (IM and OM, respectively) to a variable degree. OM permeabilization culminates in the release of proteins that normally are confined in the mitochondrial intermembrane space (IMS), including caspase activators (e.g. cytochrome c) and caspase-independent death effectors (e.g. apoptosis-inducing factor). Partial IM permeabilization disrupts mitochondrial ion and volume homeostasis and dissipates the mitochondrial transmembrane potential ( m ). The assessment of early mitochondrial alterations allows for the identification of cells that are committed to die but have not displayed yet the apoptotic phenotype. Several

show abstract

Classification of cell death: recommendations of the Nomenclature Committee on Cell Death

Cited by 1,226 publications

References 24 publications

Liberation of doxorubicin from HPMA copolymer conjugate is essential for the induction of cell cycle arrest and nuclear fragmentation in ovarian carcinoma cells

Liberation of doxorubicin from HPMA copolymer conjugate is essential for the induction of cell cycle arrest and nuclear fragmentation in ovarian carcinoma cells

DNA damaging agent-induced autophagy produces a cytoprotective adenosine triphosphate surge in malignant glioma cells

Methods for the assessment of mitochondrial membrane permeabilization in apoptosis

Contact Info

Product

Resources

About