The PARP inhibitor PJ34 modifies proliferation, NIS expression and epigenetic marks in thyroid cancer cell lines

Lavarone, Elisa; Puppin, Cinzia; Passon, Nadia; Russo, Diego; Damante, Giuseppe

doi:10.1016/j.mce.2012.08.019

Cited by 17 publications

(13 citation statements)

References 46 publications

(52 reference statements)

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“…In thyroid cancer, it has been reported that PARP1 could be a component of the sodium e iodide symporter (NIS) repressor protein complex and in various thyroid cancer cell lines PARP inhibition could increase NIS gene expression through a particular modulation of transcriptional regulatory mechanisms (Lavarone et al, 2013;Li and Ain, 2010). In our current pilot study, we found that over-expression of human AFM in PTC cells could increase the expression of PARP1 which further indicated the oncogenic effect of AFM.…”

Section: Discussionmentioning

confidence: 50%

Afamin promotes glucose metabolism in papillary thyroid carcinoma

Shen

Wei

Qiu

et al. 2016

Molecular and Cellular Endocrinology

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Section: Discussionmentioning

confidence: 50%

Afamin promotes glucose metabolism in papillary thyroid carcinoma

Shen

Wei

Qiu

et al. 2016

Molecular and Cellular Endocrinology

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“…This occurs through: (1) PARylation-induced exclusion of histone demethylase KDM5B, maintaining levels of activating histone mark K3K4me3 (82), (2) PARylation-induced dissociation of the DEK repressor, promoting loading of the RNA polymerase II mediator complex (94), and (3) creation of a PAR scaffold for retention of RNA polymerase II (95). Surprisingly, a recent report showed that inhibition of PARP-1 enzymatic activity was associated with increased H3K4me3, resulting in upregulation of sodium iodide symporter transcription and elevated radio-iodine uptake in thyroid cancer cell lines (96). This contradictory work may result from target gene specific functions of PARP-1, as the previously cited studies were focused on genes known to be positively regulated by PARP-1.…”

Section: Gene Transcriptionmentioning

confidence: 99%

Beyond DNA Repair: Additional Functions of PARP-1 in Cancer

2013

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Poly(ADP-ribose) polymerases (PARPs) are DNA-dependent nuclear enzymes that transfer negatively charged ADP-ribose moieties from cellular nicotinamide-adenine-dinucleotide (NAD+) to a variety of protein substrates, altering protein–protein and protein-DNA interactions. The most studied of these enzymes is poly(ADP-ribose) polymerase-1 (PARP-1), which is an excellent therapeutic target in cancer due to its pivotal role in the DNA damage response. Clinical studies have shown susceptibility to PARP inhibitors in DNA repair defective cancers with only mild adverse side effects. Interestingly, additional studies are emerging which demonstrate a role for this therapy in DNA repair proficient tumors through a variety of mechanisms. In this review, we will discuss additional functions of PARP-1 – including regulation of inflammatory mediators, cellular energetics and death pathways, gene transcription, sex hormone- and ERK-mediated signaling, and mitosis – and the role these PARP-1-mediated processes play in oncogenesis, cancer progression, and the development of therapeutic resistance. As PARP-1 can act in both a pro- and anti-tumor manner depending on the context, it is important to consider the global effects of this protein in determining when, and how, to best use PARP inhibitors in anticancer therapy.

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“…To test cell viability the MTT assay was used as previously described (15). The cells were seeded in 96-well plates in 200 µl medium.…”

Section: Cell Viability and Apoptosis Assaysmentioning

confidence: 99%

Epigenetic bivalent marking is permissive to the synergy of HDAC and PARP inhibitors on TXNIP expression in breast cancer cells

et al. 2015

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Abstract. Studies on stem cell differentiation led to the identification of paused genes, characterized by the contemporary presence of both activator and repressor epigenetic markers (bivalent marking). TXNIP is an oncosuppressor gene the expression of which was reduced in breast cancer. In the present study, we evaluated whether the concept of epigenetic bivalent marking can be applied to TXNIP gene in breast cancer cells. Using chromatin immunoprecipitation (ChIP), three histone modifications were investigated: two associated with transcriptional activation, lysines 9-14 acetylation of H3 histone (H3K9K14ac) and lysine 4 trimethylation of H3 histone (H3K4me3), and one associated with transcriptional silencing, lysine 27 trimethylation of H3 histone (H3K27me3). According to the bivalent marking model, TXNIP gene appears to be paused in MDA157 cells (markers of active and repressed transcription are present), but are definitively silenced in MDA468 cells (presence of only markers of transcription repression). This was proven by evaluating TXNIP mRNA and protein levels after the treatment of cell lines with a histone deacetylase inhibitor (SAHA) and a poly-ADPribose polymerases inhibitor (PJ34). In MDA157 cells, SAHA and PJ34 showed a synergistic effect: a large increment was observed in TXNIP mRNA and protein levels. By contrast, in MDA468 cells, synergy between the two compounds was not observed. Therefore, the pausing epigenetic signature was permissive for synergy between SAHA and PJ34 on TXNIP gene expression. The synergy between SAHA and PJ34 on TXNIP expression was associated with variation in cell viability and apoptosis. In MDA157 cells, but not in MDA468 cells, combined treatment of SAHA and PJ34 induced a decrease in cell viability and an increase of apoptosis. Thus, our data support the hypothesis that TXNIP is an effective target for the treatment of breast cancer.

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The PARP inhibitor PJ34 modifies proliferation, NIS expression and epigenetic marks in thyroid cancer cell lines

Cited by 17 publications

References 46 publications

Afamin promotes glucose metabolism in papillary thyroid carcinoma

Afamin promotes glucose metabolism in papillary thyroid carcinoma

Beyond DNA Repair: Additional Functions of PARP-1 in Cancer

Epigenetic bivalent marking is permissive to the synergy of HDAC and PARP inhibitors on TXNIP expression in breast cancer cells

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