The effect of the chemotherapeutic drug VP-16 on poly(ADP-ribosylation) in apoptotic HeLa cells

Negri, C.; Bernardi, Rosa; Braghetti, A.; Ricotti, G.; Scovassi, A. Ivana

doi:10.1093/carcin/14.12.2559

Cited by 35 publications

(20 citation statements)

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“…From previous studies it would appear that etoposide-induced PARP activation is dependent not only on the concentration and schedule of etoposide exposure, but also on the cell type. For example, etoposide has been found to activate PARP in HL-60, U939 and HeLa cells but not Molt 4 and CEM cells (Tanizawa et al, 1989;Kubota et al, 1990;Negri et al, 1993;Bernardi et al, 1995). Together, the failure of NU1025 to enhance etoposide cytotoxicity or DNA strand breakage, and the lack of PARP activation following etoposide treatment, indicate that PARP is not involved in etoposide cytotoxicity in L1210 cells.…”

Section: Discussionmentioning

confidence: 99%

“…It has been suggested that secondary fragmentation of DNA during apoptosis may induce PARP (Negri et al, 1993). To investigate if apoptotic DNA cleavage was responsible for the observed effects of camptothecin and etoposide on PARP activity, morphological examination of Hoechst 33258-stained cells was conducted.…”

Section: Induction Of Apoptosis By Camptothecin and Etoposidementioning

confidence: 99%

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Differential effects of the poly (ADP-ribose) polymerase (PARP) inhibitor NU1025 on topoisomerase I and II inhibitor cytotoxicity in L1210 cells in vitro

et al. 2001

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The potent novel poly(ADP-ribose) polymerase (PARP) inhibitor, NU1025, enhances the cytotoxicity of DNA-methylating agents and ionizing radiation by inhibiting DNA repair. We report here an investigation of the role of PARP in the cellular responses to inhibitors of topoisomerase I and II using NU1025. The cytotoxicity of the topoisomerase I inhibitor, camptothecin, was increased 2.6-fold in L1210 cells by co-incubation with NU1025. Camptothecin-induced DNA strand breaks were also increased 2.5-fold by NU1025 and exposure to camptothecin-activated PARP. In contrast, NU1025 did not increase the DNA strand breakage or cytotoxicity caused by the topoisomerase II inhibitor etoposide. Exposure to etoposide did not activate PARP even at concentrations that caused significant levels of apoptosis. Taken together, these data suggest that potentiation of camptothecin cytotoxicity by NU1025 is a direct result of increased DNA strand breakage, and that activation of PARP by camptothecin-induced DNA damage contributes to its repair and consequently cell survival. However, in L1210 cells at least, it would appear that PARP is not involved in the cellular response to etoposide-mediated DNA damage. On the basis of these data, PARP inhibitors may be potentially useful in combination with topoisomerase I inhibitor anticancer chemotherapy. © 2001 Cancer Research Campaign http://www.bjcancer.com

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Section: Discussionmentioning

confidence: 99%

Section: Induction Of Apoptosis By Camptothecin and Etoposidementioning

confidence: 99%

Differential effects of the poly (ADP-ribose) polymerase (PARP) inhibitor NU1025 on topoisomerase I and II inhibitor cytotoxicity in L1210 cells in vitro

et al. 2001

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“…There are several characteristic cellular and biochemical hallmarkers of apoptotic cell death, including oligonucleosomal DNA fragmentation, 45 nucleus condensation, DNA laddering, and PARP-1 cleavage. 46,47 The sequence of changes in cellular morphology of apoptosis can be summed up as (1) cell shrinkage (2) condensation, margination and fragmentation of chromatin and (3) retention of cytoplasmic organelle structure, but loss of positional interrelationships of organelles.…”

Section: Minimum Inhibitory Concentration Measurementsmentioning

confidence: 99%

Spectroscopic, Redox and Biological Studies of Push-Pull Porphyrins and Their Metal Complexes

Rajesh¹,

Rahiman²,

Bharathi³

et al. 2010

Bulletin of the Korean Chemical Society

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We have synthesized a series of push-pull porphyrins containing both donor and acceptor substituents at the mesopositions and have examined their spectral and biological properties. The push-pull porphyrins containing both strong donor NH2 and acceptor NO2 at meso-positions, in which donor group condensed with the ligand, (2,6-bis(4-methylpiperazine-1-yl-methyl)-4-formlyphenol (L) to form imine linkages with porphyrin. The Schiff base ligand 5-[4-(2,6-bis(4-methylpiperazine-1-yl-methyl)-4-iminomethylphenol)phenyl]-10,15,20-tris(4-nitrophenyl) porphyrin [an3(TPP)L] can be synthesized from 2,6-bis(4-methylpiperazine-1-yl-methyl)-4-formylphenol (L) and 5-(4-aminophenyl)-10, 15,20-tris(4-nitrophenyl)porphyrin. The push-pull porphyrin [an3(TPP)L] was metallated to get copper, nickel and zinc complexes. The spectral, electrochemical, antibacterial, antifungal and cytotoxicity properties of all the donor-acceptor push-pull porphyrins and their complexes were characterized and studied.

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“…After a 3-h treatment with 100 M VP-16, cells were allowed to recover for 3 or 24 h in normal medium before being analyzed by Western blotting to assess the phosphorylation status of hLigI. Because VP-16 is a well known apoptotic agent (Negri et al, 1993;Kaufmann, 1998), in parallel we determined the occurrence of apoptosis by following different morphological parameters such as nuclear condensation and fragmentation. A very low level of apoptosis (3.5 Ϯ 0.1%) was detectable at the end of the 3-h treatment with VP-16.…”

Section: Dephosphorylation Of Hligi In Response To Dna Damagementioning

confidence: 99%

Etoposide Induces the Dispersal of DNA Ligase I from Replication Factories

Montecucco

Rossi

Ferrari

et al. 2001

MBoC

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In eukaryotic cells DNA replication occurs in specific nuclear compartments, called replication factories, that undergo complex rearrangements during S-phase. The molecular mechanisms underlying the dynamics of replication factories are still poorly defined. Here we show that etoposide, an anticancer drug that induces double-strand breaks, triggers the redistribution of DNA ligase I and proliferating cell nuclear antigen from replicative patterns and the ensuing dephosphorylation of DNA ligase I. Moreover, etoposide triggers the formation of RPA foci, distinct from replication factories. The effect of etoposide on DNA ligase I localization is prevented by aphidicolin, an inhibitor of DNA replication, and by staurosporine, a protein kinase inhibitor and checkpoints' abrogator. We suggest that dispersal of DNA ligase I is triggered by an intra-S-phase checkpoint activated when replicative forks meet topoisomerase II-DNA-cleavable complexes. However, etoposide treatment of ataxia telangiectasia cells demonstrated that ataxiatelangiectasia-mutated activity is not required for the disassembly of replication factories and the formation of replication protein A foci.

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The effect of the chemotherapeutic drug VP-16 on poly(ADP-ribosylation) in apoptotic HeLa cells

Cited by 35 publications

References 0 publications

Differential effects of the poly (ADP-ribose) polymerase (PARP) inhibitor NU1025 on topoisomerase I and II inhibitor cytotoxicity in L1210 cells in vitro

Differential effects of the poly (ADP-ribose) polymerase (PARP) inhibitor NU1025 on topoisomerase I and II inhibitor cytotoxicity in L1210 cells in vitro

Spectroscopic, Redox and Biological Studies of Push-Pull Porphyrins and Their Metal Complexes

Etoposide Induces the Dispersal of DNA Ligase I from Replication Factories

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