Punicalagin from pomegranate promotes human papillary thyroid carcinoma BCPAP cell death by triggering ATM-mediated DNA damage response

Papillary thyroid carcinoma (PTC) etiologically occurs as a radiation-induced or sporadic malignancy. Genetic factors contributing to the susceptibility to either form remain unknown. In this retrospective case–control study, we evaluated possible associations between single-nucleotide polymorphisms (SNPs) in the candidate DNA damage response genes (ATM, XRCC1, TP53, XRCC3, MTF1) and risk of radiation-induced and sporadic PTC. A total of 255 PTC cases (123 Chernobyl radiation-induced and 132 sporadic, all in Caucasians) and 596 healthy controls (198 residents of Chernobyl areas and 398 subjects without history of radiation exposure, all Caucasians) were genotyped. The risk of PTC and SNPs interactions with radiation exposure were assessed by logistic regressions. The ATM G5557A and XRCC1 Arg399Gln polymorphisms, regardless of radiation exposure, associated with a decreased risk of PTC according to the multiplicative and dominant models of inheritance (odds ratio (OR)=0.69, 95% confidence interval (CI) 0.45–0.86 and OR=0.70, 95% CI 0.59–0.93 respectively). The ATM IVS22-77 T>C and TP53 Arg72Pro SNPs interacted with radiation (P=0.04 and P=0.01 respectively). ATM IVS22-77 associated with the increased risk of sporadic PTC (OR=1.84, 95% CI 1.10–3.24) whereas TP53 Arg72Pro correlated with the higher risk of radiogenic PTC (OR=1.80, 95% CI 1.06–2.36). In the analyses of ATM/TP53 (rs1801516/rs664677/rs609429/rs1042522) combinations, the GG/TC/CG/GC genotype strongly associated with radiation-induced PTC (OR=2.10, 95% CI 1.17–3.78). The GG/CC/GG/GG genotype displayed a significantly increased risk for sporadic PTC (OR=3.32, 95% CI 1.57–6.99). The results indicate that polymorphisms of DNA damage response genes may be potential risk modifiers of ionizing radiation-induced or sporadic PTCs.

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Ionizing radiation enhances dl922–947-mediated cell death of anaplastic thyroid carcinoma cells

Endocrine Related Cancer ◽

10.1530/erc-13-0001 ◽

2013 ◽

Vol 20 (5) ◽

pp. 633-647 ◽

Cited By ~ 13

Author(s):

Carmela Passaro ◽

Antonella Abagnale ◽

Silvana Libertini ◽

Massimiliano Volpe ◽

Ginevra Botta ◽

...

Keyword(s):

Dna Damage ◽

Cell Death ◽

Thyroid Carcinoma ◽

Viral Infection ◽

Dna Damage Response ◽

Combined Treatment ◽

Anaplastic Thyroid Carcinoma ◽

Tumor Xenograft ◽

Protective Mechanism ◽

Damage Response

dl922–947 is an oncolytic adenovirus potentially suitable for the treatment of aggressive localized tumors, such as anaplastic thyroid carcinoma (ATC). In this study, we have analyzed the effects of dl922–947 in combination with ionizing radiations, testing different schedules of administration and observing synergistic effects only when ATC cells were irradiated 24 h prior to viral infection. Cells undergoing combined treatment exhibited a marked increase in cell death and viral replication, suggesting that irradiation blocks cells in a more permissive state for viral life cycle. We also show that dl922–947 triggers a DNA damage response, characterized by mobilization of the MRN complex (composed by Mre11-Rad50-Nbs1), accumulation of γH2AX, and activation of the checkpoint kinases ataxia telangiectasia mutated (ATM) and Chk1. Based on these observations, we speculate that the DNA damage response acts as a cellular protective mechanism to hinder viral infection and replication. To confirm this hypothesis, we demonstrate that the ATM inhibitor KU55933 increased the oncolytic activity of dl922–947 and its replication. Finally, we validate the potential therapeutic use of this approach by showing in vivo that the combined treatment slows tumor xenograft growth more potently than either irradiation or infection alone.

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Apigenin induces autophagic cell death in human papillary thyroid carcinoma BCPAP cells

Food & Function ◽

10.1039/c5fo00671f ◽

2015 ◽

Vol 6 (11) ◽

pp. 3464-3472 ◽

Cited By ~ 43

Author(s):

Li Zhang ◽

Xian Cheng ◽

Yanyan Gao ◽

Jie Zheng ◽

Qiang Xu ◽

...

Keyword(s):

Cell Cycle ◽

Dna Damage ◽

Cell Death ◽

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Cell Cycle Arrest ◽

Autophagic Cell Death ◽

Ros Generation ◽

Papillary Thyroid ◽

Cycle Arrest

Apigenin-induced autophagic cell death in human papillary thyroid carcinoma BCPAP cells is associated with ROS generation, DNA damage and cell cycle arrest.

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Roles of phosphatidylinositol 3-kinase regulatory subunit alpha, activator protein-1, and programmed cell death 4 in diagnosis of papillary thyroid carcinoma

Tumor Biology ◽

10.1007/s13277-015-4476-x ◽

2015 ◽

Vol 37 (5) ◽

pp. 6519-6526 ◽

Cited By ~ 2

Author(s):

Xiaojun Chen ◽

Wenjun Wu ◽

Xiong Chen ◽

Xiaohua Gong

Keyword(s):

Cell Death ◽

Papillary Thyroid Carcinoma ◽

Programmed Cell Death ◽

Thyroid Carcinoma ◽

Regulatory Subunit ◽

Activator Protein 1 ◽

Papillary Thyroid ◽

Phosphatidylinositol 3 Kinase ◽

Activator Protein ◽

Programmed Cell Death 4

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Depletion of the DarG antitoxin in Mycobacterium tuberculosis triggers the DNA‐damage response and leads to cell death

Molecular Microbiology ◽

10.1111/mmi.14571 ◽

2020 ◽

Vol 114 (4) ◽

pp. 641-652 ◽

Cited By ~ 1

Author(s):

Anisha Zaveri ◽

Ruojun Wang ◽

Laure Botella ◽

Ritu Sharma ◽

Linnan Zhu ◽

...

Keyword(s):

Dna Damage ◽

Cell Death ◽

Mycobacterium Tuberculosis ◽

Dna Damage Response ◽

Damage Response

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RUNX Family Participates in the Regulation of p53-Dependent DNA Damage Response

International Journal of Genomics ◽

10.1155/2013/271347 ◽

2013 ◽

Vol 2013 ◽

pp. 1-12 ◽

Cited By ~ 22

Author(s):

Toshinori Ozaki ◽

Akira Nakagawara ◽

Hiroki Nagase

Keyword(s):

Cell Cycle ◽

Dna Damage ◽

Cell Death ◽

Cell Cycle Arrest ◽

Dna Damage Response ◽

Apoptotic Cell ◽

Genetic Alterations ◽

Apoptotic Cell Death ◽

Cycle Arrest ◽

Damage Response

A proper DNA damage response (DDR), which monitors and maintains the genomic integrity, has been considered to be a critical barrier against genetic alterations to prevent tumor initiation and progression. The representative tumor suppressor p53 plays an important role in the regulation of DNA damage response. When cells receive DNA damage, p53 is quickly activated and induces cell cycle arrest and/or apoptotic cell death through transactivating its target genes implicated in the promotion of cell cycle arrest and/or apoptotic cell death such asp21WAF1,BAX, andPUMA. Accumulating evidence strongly suggests that DNA damage-mediated activation as well as induction of p53 is regulated by posttranslational modifications and also by protein-protein interaction. Loss of p53 activity confers growth advantage and ensures survival in cancer cells by inhibiting apoptotic response required for tumor suppression. RUNX family, which is composed of RUNX1, RUNX2, and RUNX3, is a sequence-specific transcription factor and is closely involved in a variety of cellular processes including development, differentiation, and/or tumorigenesis. In this review, we describe a background of p53 and a functional collaboration between p53 and RUNX family in response to DNA damage.

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