Caspase-independent cell death?

Lockshin, Richard A.; Zakeri, Zahra

doi:10.1038/sj.onc.1207514

Cited by 191 publications

(147 citation statements)

References 98 publications

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“…AIF has multiple effects such as activation of endonucleases, and phosphatidyl serine exposure at the cell surface. It also induces cytochrome c release, [60][61][62] which may explain the delayed caspase-9 activation observed with 7b-OHchol in our present study.…”

Section: Discussionsupporting

confidence: 57%

Different apoptotic mechanisms are involved in the antiproliferative effects of 7β-hydroxysitosterol and 7β-hydroxycholesterol in human colon cancer cells

et al. 2004

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Plant sterols are found in fruits and vegetables. Their cholesterol-lowering effect is well documented. Our study aimed at comparing antiproliferative effects of 7b-hydroxysitosterol (7b-OHsito) versus 7b-hydroxycholesterol (7b-OHchol) on the human colon cancer cell line Caco-2. When cells were exposed for 32 h to 60 lM 7b-OHsito or to 30 lM 7b-OHchol, both compounds caused 50% growth inhibition. Cells treated with 7b-OHsito showed enhanced caspase-9 and -3 activities followed by DNA fragmentation. In contrast, 7b-OHchol did not activate caspase-3 and activation of caspase-9 and DNA fragmentation were delayed. The treatment of cells with the caspase inhibitor Z-VAD.fmk retarded the 7b-OHsito-induced apoptotic process but not that triggered by 7b-OHchol. Our data suggest that the two compounds in spite of their structural similarities target different cellular pathways, which lead to cell death.

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Section: Discussionsupporting

confidence: 57%

Different apoptotic mechanisms are involved in the antiproliferative effects of 7β-hydroxysitosterol and 7β-hydroxycholesterol in human colon cancer cells

et al. 2004

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“…1 It is also argued that physiological cell deaths exist that do not appear to be typical apoptosis or dependent on the caspase activation. 47 Appearance of these complex death forms can be explained by interception of active cellular death processes by, for example, oxygen-radical scavengers and inhibition of caspase or PARP. [48][49][50] Our results support the hypothesis that necrosis and typical apoptosis are two extremes of a spectrum of death programs varying with the strength of the death stimulus.…”

Section: Discussionmentioning

confidence: 99%

“…1 It is noted that mitochondria play an important role in necrosis as well as apoptosis. 1,47 As PTD-FNK was shown to localize in the mitochondria, 17,18 further studies on the function of PTD-FNK would provide insight into the correlation between apoptosis and necrosis. Since FNK exhibited clearer results than Bcl-x L , FNK will be useful for investigating this issue in future.…”

Section: Discussionmentioning

confidence: 99%

Zonal necrosis prevented by transduction of the artificial anti-death FNK protein

et al. 2005

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Protection of cells from necrosis would be important for many medical applications. Here, we show protein transduction domain (PTD)-FNK therapeutics based on protein transduction to prevent necrosis and acute hepatic injury with zonal death induced by carbon tetrachloride (CCl 4 ). PTD-FNK is a fusion protein comprising the HIV/Tat PTD and FNK, a gain-offunction mutant of anti-apoptotic Bcl-x L . PTD-FNK protected hepatoma HepG2 from necrotic death induced by CCl 4 , and additionally, increased the apoptotic population among cells treated with CCl 4 . A concomitant treatment with a pancaspase inhibitor Z-VAD-FMK (N-benzyloxycarbonyl-Val-AlaAsp-fluoromethylketone), which alone could not prevent the necrosis, protected these cells from the apoptosis. When preinjected intraperitoneally, PTD-FNK markedly reduced zonal liver necrosis caused by CCl 4 . Moreover, injection of PTD-FNK accompanied by Z-VAD-FMK suppressed necrotic injury even after CCl 4 administration. These results suggest that PTD-FNK has great potential for clinical applications to prevent cell death, whether from apoptosis or necrosis, and organ failure.

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“…Both pathways converge and activate executioner caspase-3, which then cleaves intracellular protein substrates and causes cell death. There is now accumulating evidence indicating that PCD can also occur in complete absence and independently of caspase activation (Johnson, 2000;Jaattela and Tschopp, 2003;Lockshin and Zakeri, 2004;Broker et al, 2005). Several models of caspase-independent PCD have been described.…”

Section: Introductionmentioning

confidence: 99%

CD44 ligation induces caspase-independent cell death via a novel calpain/AIF pathway in human erythroleukemia cells

et al. 2006

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Ligation of the cell surface molecule CD44 by anti-CD44 monoclonal antibodies (mAbs) has been shown to induce cell differentiation, cell growth inhibition and in some cases, apoptosis in myeloid leukemic cells. We report, herein, that exposure of human erythroleukemic HEL cells to the anti-CD44 mAb A3D8 resulted in cell growth inhibition followed by caspase-independent apoptosis-like cell death. This process was associated with the disruption of mitochondrial membrane potential (DWm), the mitochondrial release of apoptosis-inducing factor (AIF), but not of cytochrome c, and the nuclear translocation of AIF. All these effects including cell death, loss of mitochondrial DWm and AIF release were blocked by pretreatment with the poly (ADP-ribose) polymerase inhibitor isoquinoline. A significant protection against cell death was also observed by using small interfering RNA for AIF. Moreover, we show that calpain protease was activated before the appearance of apoptosis, and that calpain inhibitors or transfection of calpain-siRNA decrease A3D8-induced cell death, and block AIF release. These data suggest that CD44 ligation triggers a novel caspaseindependent cell death pathway via calpain-dependent AIF release in erythroleukemic HEL cells.

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Caspase-independent cell death?

Cited by 191 publications

References 98 publications

Different apoptotic mechanisms are involved in the antiproliferative effects of 7β-hydroxysitosterol and 7β-hydroxycholesterol in human colon cancer cells

Different apoptotic mechanisms are involved in the antiproliferative effects of 7β-hydroxysitosterol and 7β-hydroxycholesterol in human colon cancer cells

Zonal necrosis prevented by transduction of the artificial anti-death FNK protein

CD44 ligation induces caspase-independent cell death via a novel calpain/AIF pathway in human erythroleukemia cells

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