Mitochondrial changes during the apoptotic process of HeLa cells exposed to cisplatin

Meléndez-Zajgla, Jorge; Cruz, Elizabeth; Maldonado, V. Calatayud; Espinoza, Ana Maria

doi:10.1080/15216549900201853

Cited by 16 publications

(13 citation statements)

References 6 publications

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“…In all cases, the processing of procaspase-8 was either preceded or paralleled by mitochondrial permeability transition. These results suggest that the mitochondrial apoptosome is a main player in drug-induced apoptosis of B-lymphoid cells, thereby confirming other data that point to the critical role for mitochondria in the apoptotic pathways of other cell types, such as HeLa cells 37 and malignant melanoma. 48 Caspases with long prodomains, such as caspase-8, are generally considered to be upstream (inducer) caspases because of their ability to associate with cell surface death-receptor molecules.…”

Section: Discussionsupporting

confidence: 76%

“…As shown in Figure 8C, Taxol-and epirubicin-induced apoptosis was not significantly influenced by the overexpression of FADDdn. In recent publications, the critical role of mitochondrial damage for drug-induced apoptosis 36,37 and CD95-dependent signaling to mitochondria through caspase-8-mediated cleavage of Bid has been demonstrated. 38 We thus measured mitochondrial activation after treatment with Taxol and epirubicin in our experimental system.…”

Section: Activation Of Caspase-8 In B-lymphoid Cells 1383mentioning

confidence: 99%

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Activation of caspase-8 in drug-induced apoptosis of B-lymphoid cells is independent of CD95/Fas receptor-ligand interaction and occurs downstream of caspase-3

Wieder

Eßmann

Prokop

et al. 2001

Blood

231

201

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The activation of caspase-8, a crucial upstream mediator of death receptor signaling, was investigated in epirubicinand Taxol IntroductionApoptosis, a morphologically and biochemically defined form of cell death, 1 plays a role in a wide variety of biologic systems, including tissue homeostasis and regulation of the immune system. 2,3 The process is a highly orchestrated cellular pathway leading to activation of the downstream death machinery. The central mediator and executioner of the death machinery is a proteolytic system involving a family of cysteinyl proteases, called caspases (for review, see Thornberry and Lazebnik 4 ). Triggering of the apoptotic cascade by different death stimuli, such as ionizing radiation 5 and chemotherapeutic drugs, 6 culminates in caspasedependent cleavage of a set of regulatory proteins, degradation of cellular DNA, and complete disassembly of the cell. Thus far, 14 caspase family members have been identified, and some of them, such as caspase-8, mediate apoptotic signals after the activation of death receptors. 7,8 Others, such as caspase-9, are part of the apoptosome and play a role in signal transduction after mitochondrial damage. 9 Recently, an endoplasmic-reticulum-specific pathway of apoptosis has been described that is mediated by caspase-12. 10 Previous data suggest that cytotoxic drugs induce cell death through CD95/Fas-CD95 ligand interaction, 11 and the relevance of this particular death pathway has been shown, for instance, in doxorubicin-induced apoptosis of leukemic T cells. 12 However, other groups were unable to confirm these findings and showed CD95/Fas-independent induction of apoptosis by chemotherapeutic drugs-for example, doxorubicin and etoposide-in Tlymphoma cells. 13,14 The finding that CD95/Fas-signaling and DNA damage induce different apoptosis-signaling pathways has also been shown in a murine and a human B-lymphoma cell line. 15 Furthermore, experimental evidence has been provided that neither FADD 16 nor caspase-8 17 is required for drug-induced apoptosis.In B cells, the induction of apoptosis plays important roles in humoral immunity. In this context, it has been shown that the antigen receptor BCR and the CD95/Fas receptor transduce pro-apoptotic signals in mature B cells (for review, see Tsubata 18 ). We previously showed that activation-induced apoptosis of normal and malignant B lymphocytes upon antigen-receptor ligation is independent of CD95/Fas and CD95/Fas ligand. 19 This has been confirmed by another study demonstrating that B-cell receptormediated apoptosis, in contrast to activation-induced T-cell apoptosis, is not mediated through known death receptor systems, nor does it involve the initial activation of caspase-8. 20 We nevertheless For personal use only. on May 12, 2018. by guest www.bloodjournal.org From observed that drug treatment leads to processing and activation of procaspase-8. We therefore focused our interest on the specific mechanisms leading to apoptotic death after the treatment of immature and mature B-lymphoma cells wi...

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Section: Discussionsupporting

confidence: 76%

Section: Activation Of Caspase-8 In B-lymphoid Cells 1383mentioning

confidence: 99%

Activation of caspase-8 in drug-induced apoptosis of B-lymphoid cells is independent of CD95/Fas receptor-ligand interaction and occurs downstream of caspase-3

Wieder

Eßmann

Prokop

et al. 2001

Blood

231

201

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“…42 The profiles of JC-1 fluorescence of mock-or AAV-2-infected HeLa cells, either untreated or exposed to cisplatin, were compared (Fig. 4a,b).…”

Section: Aav-2 Infection Enhances Cisplatin-induced Depolarization Ofmentioning

confidence: 99%

Enhancement of cisplatin‐induced apoptosis by infection with adeno‐associated virus type 2

Duverger

Sartorius

Klein-Bauernschmitt

et al. 2001

Intl Journal of Cancer

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The non-pathogenic human adeno-associated virus, AAV, has been shown to sensitize human cancer cells and experimental tumors towards the action of chemotherapeutic agents such as cisplatin. Since chemotherapeutic drugs mainly involve the induction of apoptosis, we investigated whether 1 possible mechanism of AAV-mediated sensitization of human tumor cells may result from an enhancement of cisplatin-induced apoptosis. In HeLa and A549 cells, infection with AAV type 2 (AAV-2) increased cisplatin-induced DNA fragmentation but had no cytotoxic effect by itself. This enhanced apoptosis appeared to be mediated at least in part by a component of the viral capsid since empty or UVinactivated AAV-2 particles were also able to boost cisplatininduced DNA fragmentation. Interestingly, these effects were not observed after infection with AAV type 5 (AAV-5) or the autonomous parvovirus, H-1. AAV-2-mediated enhancement of apoptosis was not associated with a modification of the expression of CD95 ligand, CD95 receptor or other death receptors, as shown by RT-PCR and RNase protection assay. In contrast, using the mitochondrial fluorescent dye, JC-1 in flow cytometry, AAV-2 infection was found to further reduce the mitochondrial transmembrane potential after treatment with cisplatin in a caspase-independent manner, suggesting that increase of apoptosis by AAV-2 occurred at the mitochondrial level. In contrast, in cells of the small cell lung cancer line, P693, an enhancement of cisplatininduced DNA fragmentation was not observed after infection with AAV-2. In these cells, sensitization to cisplatin-toxicity was associated with cell cycle arrest in G2/M. The data indicate that in the absence of viral gene expression, AAV-2-mediated sensitization to cisplatin involves multiple cellular pathways promoting cell death signals in a cell type-dependent manner. The results further support that AAV-2 particles may be appropriate adjuvants for improving cancer chemotherapy and may also have consequences regarding AAV-2-based vectors for gene therapy.

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“…60,61 Cis induces remarkable mitochondrial changes in HeLa cells. 62 Altogether, the combination of Cis and rGO-AgNPs causes loss of MMP and eventually leads to apoptosis.…”

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confidence: 99%

Combination of graphene oxide–silver nanoparticle nanocomposites and cisplatin enhances apoptosis and autophagy in human cervical cancer cells

Yuan¹,

Gurunathan²

2017

IJN

109

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Background Cisplatin (Cis) is a widely used chemotherapeutic drug for treating a variety of cancers, due to its ability to induce cell death in cancer cells significantly. Recently, graphene and its modified nanocomposites have gained much interest in cancer therapy, due to their unique physicochemical properties. The objective of this study was to investigate the combination effect of Cis and a reduced graphene oxide–silver nanoparticle nanocomposite (rGO-AgNPs) in human cervical cancer (HeLa) cells. Materials and methods We synthesized AgNPs, rGO, and rGO-AgNP nanocomposites using C-phycocyanin. The synthesized nanomaterials were characterized using various analytical techniques. The anticancer properties of the Cis, rGO-AgNPs, and combination of Cis and rGO-AgNPs were evaluated using a series of cellular assays, such as cell viability, cell proliferation, LDH leakage, reactive oxygen species generation, and cellular levels of oxidative and antioxidative stress markers such as malondialdehyde, glutathione, SOD, and CAT. The expression of proapoptotic, antiapoptotic, and autophagy genes were measured using real-time reverse-transcription polymerase chain reaction. Results The synthesized AgNPs were well dispersed, homogeneous, and spherical, with an average size of 10 nm and uniformly distributed on graphene sheets. Cis, GO, rGO, AgNPs, and rGO-AgNPs inhibited cell viability in a dose-dependent manner. The combination of Cis and rGO-AgNPs showed significant effects on cell proliferation, cytotoxicity, and apoptosis. The combination of Cis and rGO-AgNPs had more pronounced effects on the expression of apoptotic and autophagy genes, and also significantly induced the accumulation of autophagosomes and autophagolysosomes, which was associated with the generation of reactive oxygen species. Conclusion Our findings substantiated rGO-AgNPs strongly potentiating Cis-induced cytotoxicity, apoptosis, and autophagy in HeLa cells, and hence rGO-AgNPs could be potentially applied to cervical cancer treatment as a powerful synergistic agent with Cis or any other chemotherapeutic agents.

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Mitochondrial changes during the apoptotic process of HeLa cells exposed to cisplatin

Cited by 16 publications

References 6 publications

Activation of caspase-8 in drug-induced apoptosis of B-lymphoid cells is independent of CD95/Fas receptor-ligand interaction and occurs downstream of caspase-3

Activation of caspase-8 in drug-induced apoptosis of B-lymphoid cells is independent of CD95/Fas receptor-ligand interaction and occurs downstream of caspase-3

Enhancement of cisplatin‐induced apoptosis by infection with adeno‐associated virus type 2

Combination of graphene oxide–silver nanoparticle nanocomposites and cisplatin enhances apoptosis and autophagy in human cervical cancer cells

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Mitochondrial changes during the apoptotic process of HeLa cells exposed to cisplatin

Cited by 16 publications

References 6 publications

Activation of caspase-8 in drug-induced apoptosis of B-lymphoid cells is independent of CD95/Fas receptor-ligand interaction and occurs downstream of caspase-3

Activation of caspase-8 in drug-induced apoptosis of B-lymphoid cells is independent of CD95/Fas receptor-ligand interaction and occurs downstream of caspase-3

Enhancement of cisplatin‐induced apoptosis by infection with adeno‐associated virus type 2

Combination of graphene oxide&ndash;silver nanoparticle nanocomposites and cisplatin enhances apoptosis and autophagy in human cervical cancer cells

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Combination of graphene oxide–silver nanoparticle nanocomposites and cisplatin enhances apoptosis and autophagy in human cervical cancer cells