Evidence of a lysosomal pathway for apoptosis induced by the synthetic retinoid CD437 in human leukemia HL-60 cells

Zang, Yan; Beard, Richard L.; Chandraratna, Roshantha A.S.; Kang, Jing

doi:10.1038/sj.cdd.4400843

Cited by 118 publications

(92 citation statements)

References 34 publications

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“…Generation of reactive oxygen species has been reported for CD437. 4,24 However, in our cell system, we did not detect modifications of mitochondrial trans-membrane potential nor ROS generation by ST1926 after 3-6 h exposure (data not shown). In keeping with this finding was the inability of antioxidant agents (e.g.…”

Section: Discussionmentioning

confidence: 62%

“…Indeed, atypical retinoids exert growth-inhibitory activity and induce apoptosis in retinoid-resistant cells, and these cellular effects cannot be blocked by RARantagonists. [2][3][4] Multiple mechanisms, including activation of JNK and p38, have been implicated in apoptosis induced by atypical retinoids. 5 However, the mechanism of the growthinhibitory activity and the cellular basis of the broad spectrum of activity of these compounds remain largely unknown.…”

Section: Introductionmentioning

confidence: 99%

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Induction of apoptosis and stress response in ovarian carcinoma cell lines treated with ST1926, an atypical retinoid

et al. 2003

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To understand the molecular mechanisms mediating apoptosis induction by a novel atypical retinoid, ST1926, the cellular response to drug treatment was investigated in IGROV-1 ovarian carcinoma cells carrying wild-type p53 and a cisplatin-resistant p53 mutant subline (IGROV-1/Pt1). Despite a similar extent of drug-induced DNA strand breaks, the level of apoptosis was substantially higher in p53 wild-type cells. p53 activation and early upregulation of p53-target genes were consistent with p53-dependent apoptosis in IGROV-1 cells. Stress-activated protein kinases were activated in both cell lines in response to ST1926. This event and activation of AP-1 were more pronounced in IGROV-1/Pt1 cells, in which the modulation of DNA repair-associated genes suggests an increased ability to repair DNA damage. Inhibition of JNK or p38 stimulated ST1926-induced apoptosis only in IGROV-1 cells, whereas inhibition of ERKs enhanced apoptosis in both the cell lines. Such a pattern of cellular response and modulation of genes implicated in DNA damage response supports that the genotoxic stress is a critical event mediating drug-induced apoptosis. The results are consistent with apoptosis induction through p53-dependent andindependent pathways, regulated by MAP kinases, which likely play a protective role.

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Section: Discussionmentioning

confidence: 62%

Section: Introductionmentioning

confidence: 99%

Induction of apoptosis and stress response in ovarian carcinoma cell lines treated with ST1926, an atypical retinoid

et al. 2003

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“…5,8,9 Why should inhibition of just one cathepsin be detrimental for NB cell survival? It has been previously shown that deficiency of CD or inhibition of either CD or CB does not compromise overall turnover of long-lived proteins.…”

Section: Discussionmentioning

confidence: 99%

“…3,4 Recently, proteases resident within the endosomal-lysosomal compartment (cathepsins) have also been associated with apoptosis. [5][6][7][8][9] These studies demonstrated the need for a cathepsin-mediated proteolytic event in the apoptotic pathway triggered by cytokines or antiblastic drugs. In addition, the active participation of the autophagic proteolytic pathway, particularly of lysosomal cathepsins B and D (CB, CD), has been envisaged in rat pheochromocytoma PC12 cell death after nutrient and serum factor deprivation.…”

mentioning

confidence: 94%

Lysosomal proteases as potential targets for the induction of apoptotic cell death in human neuroblastomas

Castino¹,

Pace²,

Démoz³

et al. 2001

Intl Journal of Cancer

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Neuroblastoma is the most common type of cancer in infants. In children this tumor is particularly aggressive; despite various new therapeutic approaches, it is associated with poor prognosis. Given the importance of endosomallysosomal proteolysis in cellular metabolism, we hypothesized that inhibition of lysosomal protease would impact negatively on neuroblastoma cell survival. Treatment with E-64 or CA074Me (2 specific inhibitors of cathepsin B) or with pepstatin A (a specific inhibitor of cathepsin D) was cytotoxic for 2 neuroblastoma cell lines having different degrees of malignancy. Cell death was associated with condensation and fragmentation of chromatin and externalization of plasma membrane phosphatidylserine, 2 hallmarks of apoptosis. Concomitant inhibition of the caspase cascade protected neuroblastoma cells from cathepsin inhibitor-induced cytotoxicity. These data indicate that prolonged inhibition of the lysosomal proteolytic pathway is incompatible with cell survival, leading to apoptosis of neuroblastoma cells, and that the cathepsin-mediated and caspase-mediated proteolytic systems are connected and cooperate in the regulation of such an event. Since modern antitumor chemotherapy is aimed at restoring the normal rate of apoptosis in neoplastic tissues, the demonstration that endosomal-lysosomal cathepsins are involved in this process may constitute a basis for novel strategies that include cathepsin inhibitors in the therapeutic regimen. © 2002 Wiley-Liss, Inc. Key words: apoptosis; neuroblastoma; caspases; cathepsins; protease inhibitorsAltered regulation of cell survival and death, including apoptosis, is considered an important factor in tumor development and progression, as well as in the response to antineoplastic therapy. 1,2 The molecular pathways controlling apoptosis include a complex network of intracellular proteases that act in an orderly sequence on cellular substrates and lead to characteristic modifications of cell morphology with eventual DNA cleavage and apoptotic body formation. Several proteolytic systems have been shown to participate in the apoptotic process, depending on the cell type and stimuli adopted. With few exceptions, the caspase system seems to be the most universally involved one. 3,4 Recently, proteases resident within the endosomal-lysosomal compartment (cathepsins) have also been associated with apoptosis. 5-9 These studies demonstrated the need for a cathepsin-mediated proteolytic event in the apoptotic pathway triggered by cytokines or antiblastic drugs. In addition, the active participation of the autophagic proteolytic pathway, particularly of lysosomal cathepsins B and D (CB, CD), has been envisaged in rat pheochromocytoma PC12 cell death after nutrient and serum factor deprivation. In this model of caspasedependent apoptosis, CD acted as a death factor, whereas CB acted as a pro-survival factor. 10 We followed an opposite approach, assuming that the endosomal-lysosomal proteolytic pathway serves crucial functions for cell viability. Indeed, experiments usi...

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“…In contrast, p53-induced cell death involved early lysosomal damage, followed by mitochondria damage, which was blocked by BHA (25). Cathepsin D release preceded ROI production in the course of retinoid-induced HL60 cell death (28). In TWEAK-stimulated hFn14/L5178Y cells, cathepsin B release was abrogated by antioxidant BHA (Fig.…”

Section: Characterization Of Tweak-induced Cell Death In Hfn14 Transfmentioning

confidence: 93%

Fibroblast Growth Factor-Inducible 14 Mediates Multiple Pathways of TWEAK-Induced Cell Death

Nakayama¹,

Ishidoh²,

Kojima³

et al. 2003

The Journal of Immunology

132

133

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TWEAK, a TNF family member, is produced by IFN-γ-stimulated monocytes and induces multiple pathways of cell death, including caspase-dependent apoptosis, cathepsin B-dependent necrosis, and endogenous TNF-α-mediated cell death, in a cell type-specific manner. However, the TWEAK receptor(s) that mediates these multiple death pathways remains to be identified. Recently, fibroblast growth factor-inducible 14 (Fn14) has been identified to be a TWEAK receptor, which was responsible for TWEAK-induced proliferation of endothelial cells and angiogenesis. Because Fn14 lacks the cytoplasmic death domain, it remains unclear whether Fn14 can also mediate the TWEAK-induced cell death. In this study, we demonstrated that TWEAK could induce apoptotic cell death in Fn14 transfectants. A pan-caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone, rather sensitized the Fn14 transfectants to TWEAK-induced cell death by necrosis via reactive oxygen intermediates and cathepsin B-dependent pathway. By using newly generated agonistic anti-Fn14 mAbs, we also observed that Fn14 is constitutively expressed on the cell surface of all TWEAK-sensitive tumor cell lines, and can transmit the multiple death signals. Moreover, an anti-Fn14 mAb that blocks TWEAK-Fn14 interaction could totally abrogate TWEAK binding and TWEAK-induced cell death in all TWEAK-sensitive tumor cell lines. These results revealed that the multiple pathways of TWEAK-induced cell death are solely mediated by Fn14.

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Evidence of a lysosomal pathway for apoptosis induced by the synthetic retinoid CD437 in human leukemia HL-60 cells

Cited by 118 publications

References 34 publications

Induction of apoptosis and stress response in ovarian carcinoma cell lines treated with ST1926, an atypical retinoid

Induction of apoptosis and stress response in ovarian carcinoma cell lines treated with ST1926, an atypical retinoid

Lysosomal proteases as potential targets for the induction of apoptotic cell death in human neuroblastomas

Fibroblast Growth Factor-Inducible 14 Mediates Multiple Pathways of TWEAK-Induced Cell Death

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