An assessment of poly (ADP‐ribose) polymerase‐1 role in normal and cancer cells

Kumar, Manoj; Jaiswal, Rishi Kumar; Yadava, Pramod Kumar; Singh, Rana P.

doi:10.1002/biof.1688

Cited by 23 publications

(19 citation statements)

References 123 publications

(256 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In order to evaluate the proapoptotic properties of the newly synthesized derivatives, we analyzed the level of cleaved PARP1 [c-PARP1, nuclear poly (ADP-ribose) polymerase 1], the hallmark of apoptotic cells [64]. After 24-h treatment, the significantly elevated level of c-PARP1 was detected only in MDA-MB-231 cells with the highest relative level of 7.14 detected in cells treated with compound 6c (Figure 7).…”

Section: Induction Of Apoptosis In Mcf-7 and Mda-mb-231 Cellsmentioning

confidence: 99%

Synthesis of Novel Acyl Derivatives of 3-(4,5,6,7-Tetrabromo-1H-benzimidazol-1-yl)propan-1-ols—Intracellular TBBi-Based CK2 Inhibitors with Proapoptotic Properties

Chojnacki

Wińska

Karatsai

et al. 2021

IJMS

View full text Add to dashboard Cite

Protein kinase CK2 has been considered as an attractive drug target for anti-cancer therapy. The synthesis of N-hydroxypropyl TBBi and 2MeTBBi derivatives as well as their respective esters was carried out by using chemoenzymatic methods. Concomitantly with kinetic studies toward recombinant CK2, the influence of the obtained compounds on the viability of two human breast carcinoma cell lines (MCF-7 and MDA-MB-231) was evaluated using MTT assay. Additionally, an intracellular inhibition of CK2 as well as an induction of apoptosis in the examined cells after the treatment with the most active compounds were studied by Western blot analysis, phase-contrast microscopy and flow cytometry method. The results of the MTT test revealed potent cytotoxic activities for most of the newly synthesized compounds (EC50 4.90 to 32.77 µM), corresponding to their solubility in biological media. We concluded that derivatives with the methyl group decrease the viability of both cell lines more efficiently than their non-methylated analogs. Furthermore, inhibition of CK2 in breast cancer cells treated with the tested compounds at the concentrations equal to their EC50 values correlates well with their lipophilicity since derivatives with higher values of logP are more potent intracellular inhibitors of CK2 with better proapoptotic properties than their parental hydroxyl compounds.

show abstract

Section: Induction Of Apoptosis In Mcf-7 and Mda-mb-231 Cellsmentioning

confidence: 99%

Synthesis of Novel Acyl Derivatives of 3-(4,5,6,7-Tetrabromo-1H-benzimidazol-1-yl)propan-1-ols—Intracellular TBBi-Based CK2 Inhibitors with Proapoptotic Properties

Chojnacki

Wińska

Karatsai

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…The antiapoptotic Bcl-2 and proapoptotic Bax are important players in intrinsic apoptosis ( Cui and Placzek, 2018 ; Carpenter and Brady, 2021 ). PARP is a multifunction protein associated with DNA damage and cell apoptosis ( Kumar et al, 2020 ). By combining the detection of these biomarkers, we found that circ_DOCK1 mitigated H 2 O 2 -driven proliferation inhibition and apoptosis promotion in HBVSMCs.…”

Section: Discussionmentioning

confidence: 99%

CircRNA DOCK1 Regulates miR-409-3p/MCL1 Axis to Modulate Proliferation and Apoptosis of Human Brain Vascular Smooth Muscle Cells

Ding

Wang

Han

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

BackgroundIntracranial aneurysm is an abnormal expansion in the intracranial arteries, which is associated with growth and apoptosis of vascular smooth muscle cells. Circular RNAs (circRNAs) have implicated in the progression of intracranial aneurysms. The purpose of this paper is to study the function and mechanism of circRNA dedicator of cytokinesis 1 (circ_DOCK1) in regulating proliferation and apoptosis of human brain vascular smooth muscle cells (HBVSMCs).MethodsHBVSMCs were exposed to hydrogen peroxide (H2O2). Cell proliferation and apoptosis were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and flow cytometry, respectively. Circ_DOCK1, microRNA (miR)-409-3p, and myeloid cell leukemia sequence 1 (MCL1) levels were examined by quantitative reverse transcription polymerase chain reaction or western blotting. The target association was assessed by dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation assays.ResultsExposure to H2O2 decreased proliferation and increased apoptosis of HBVSMCs. Circ_DOCK1 expression was reduced in H2O2-treated HBVSMCs. Circ_DOCK1 overexpression rescued H2O2-caused reduction of proliferation and PCNA expression and attenuated H2O2-induced apoptosis and expression of Bcl-2, Bax, and cleaved PARP. MiR-409-3p was targeted by circ_DOCK1 and upregulated in H2O2-treated HBVSMCs. MiR-409-3p upregulation mitigated the role of circ_DOCK1 in proliferation and apoptosis of H2O2-treated HBVSMCs. MCL1 was targeted via miR-409-3p and downregulated via H2O2 treatment. Circ_DOCK1 overexpression enhanced MCL1 expression via modulating miR-409-3p. MiR-409-3p knockdown weakened H2O2-induced proliferation reduction and apoptosis promotion via regulating MCL1.ConclusionCirc_DOCK1 overexpression mitigated H2O2-caused proliferation inhibition and apoptosis promotion in HBVSMCs by modulating miR-409-3p/MCL1 axis.

show abstract

“…Recent studies also associate it with epithelial to mesenchymal transition (EMT), a biological phenomenon involved in the early progression of cancer metastasis, and the modulation of EMT regulators like Vimentin, Claudin-1 and other transcription factors, playing a dual role in EMT. In this sense, PARP-1 became a special target for cancer treatment, and several inhibitors of PARP-1 like Olaparib, Rucaparib and Veliparib are already in use [8].…”

Section: Discussionmentioning

confidence: 99%

“…While it is argued that for minor DNA damage, cancer cells activate PARP-1 to help in the cell survival by repairing the mild DNA lesions, for high-level DNA damage PARP-1 is overactivated and uses NAD+ as a donor of ADP ribose for ADP-ribosylation, driving the cell into an imbalance of NAD+/ATP ratio, NAD depletion and eventually resulting in an energy-deprived necrosis [8,52,53]. Remarkably, each cell line seems to be "specialized" on PARP1 and/or PARP2 for the aforementioned repair mechanisms, and a ratio between them proportional to the degree of the DNA damage and the mutagenic effect of each alkylating compound is formed (Figures 5 and 7).…”

Section: Discussionmentioning

confidence: 99%

“…This catalytic domain helps in the ADPribosylation of various acceptor proteins using nicotinamide adenine dinucleotide (NAD+) as a donor for ADP-ribose. PARP-1 and PARP-2 carry out 80% of the poly-ADP-ribosylation of cellular protein [8]. Poly-ADP-ribosylation of nuclear proteins, a post-translational event, occurs in response to DNA damage.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cytocidal Antitumor Effects against Human Ovarian Cancer Cells Induced by B-Lactam Steroid Alkylators with Targeted Activity against Poly (ADP-Ribose) Polymerase (PARP) Enzymes in a Cell-Free Assay

et al. 2021

View full text Add to dashboard Cite

We evaluated three newly synthesized B-lactam hybrid homo-aza-steroidal alkylators (ASA-A, ASA-B and ASA-C) for their PARP1/2 inhibition activity and their DNA damaging effect against human ovarian carcinoma cells. These agents are conjugated with an alkylating component (POPA), which also served as a reference molecule (positive control) and were tested against four human ovarian cell lines in vitro (UWB1.289 + BRCA1, UWB1.289, SKOV-3 and OVCAR-3). The studied compounds were thereafter compared to 3-AB, a known PARP inhibitor, as well as to Olaparib, a standard third-generation PARP inhibitor, on a PARP assay investigating their inhibitory potential. Finally, a PARP1 and PARP2 mRNA expression analysis by qRT-PCR was produced in order to measure the absolute and the relative gene expression (in mRNA transcripts) between treated and untreated cells. All the investigated hybrid steroid alkylators and POPA decreased in vitro cell growth differentially, according to the sensitivity and different gene characteristics of each cell line, while ASA-A and ASA-B presented the most significant anticancer activity. Both these compounds induced PARP1/2 enzyme inhibition, DNA damage (alkylation) and upregulation of PARP mRNA expression, for all tested cell lines. However, ASA-C underperformed on average in the above tasks, while the compound ASA-B induced synthetic lethality effects on the ovarian cancer cells. Nevertheless, the overall outcome, leading to a drug-like potential, provides strong evidence toward further evaluation.

show abstract

An assessment of poly (ADP‐ribose) polymerase‐1 role in normal and cancer cells

Cited by 23 publications

References 123 publications

Synthesis of Novel Acyl Derivatives of 3-(4,5,6,7-Tetrabromo-1H-benzimidazol-1-yl)propan-1-ols—Intracellular TBBi-Based CK2 Inhibitors with Proapoptotic Properties

Synthesis of Novel Acyl Derivatives of 3-(4,5,6,7-Tetrabromo-1H-benzimidazol-1-yl)propan-1-ols—Intracellular TBBi-Based CK2 Inhibitors with Proapoptotic Properties

CircRNA DOCK1 Regulates miR-409-3p/MCL1 Axis to Modulate Proliferation and Apoptosis of Human Brain Vascular Smooth Muscle Cells

Cytocidal Antitumor Effects against Human Ovarian Cancer Cells Induced by B-Lactam Steroid Alkylators with Targeted Activity against Poly (ADP-Ribose) Polymerase (PARP) Enzymes in a Cell-Free Assay

Contact Info

Product

Resources

About