DNA damage response – A double-edged sword in cancer prevention and cancer therapy

Tian, Hui; Z, Gao; Li, Huizhong; Zhang, Baofu; Wang, Gang; Zhang, Qing; Pei, Dong‐Sheng; Zheng, Junnian

doi:10.1016/j.canlet.2014.12.038

Cited by 163 publications

(107 citation statements)

References 72 publications

Supporting

Mentioning

107

Contrasting

Order By: Relevance

“…However, defect in apoptosis can cause cancer and the suppression of apoptosis during carcinogenesis may play a crucial role in the development of some cancer types (2). Apoptosis is characterized by different morphological changes, such as cell membrane blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation and chromosomal DNA fragmentation (3,4). In order to promote phagocytosis of apoptotic cells by macrophages, apoptotic cells present specific membrane morphologies to activate this process.…”

Section: Targets Of Mdr Cancer Cellsmentioning

confidence: 99%

Identification of Important Compounds Isolated from Natural Sources that Have Activity Against Multidrug-resistant Cancer Cell Lines: Effects on Proliferation, Apoptotic Mechanism and the Efflux Pump Responsible for Multi-resistance Phenotype

Amaral

Spengler

Molnár

2016

View full text Add to dashboard Cite

Abstract. The focus of this mini-review is to identify non-toxic compounds isolated from natural sources (plants) that exhibit specific activity against efflux pumps of specific multidrugresistant (MDR) cancer cell lines, inhibit proliferation of the MDR cancer cell lines and inhibit the activity of overexpressed efflux pumps of the MDR cancer cell line.Therapy of cancer, if not completely effective, results in the overexpression of genes that code for efflux pumps that extrude the noxious agent (anticancer drug) before it reaches its intended target of the cancer cell (1). The overexpressed efflux pump renders the cancer cell immune to not only the initial drug used in therapy but to a wide range of unrelated noxious compounds (1). The arising of this multidrugresistant (MDR) phenotype makes therapy highly problematic and the end result is that the patient succumbs to the disease (1). Therefore, it is the consensus of many that therapy of MDR cancer may succeed if the responsible efflux pump is inhibited from its activity, therefore, affording the increased concentration of anticancer drug to a level consistent with its toxic targeted action needed to kill the cancer cell. To this extent, over 100,000 synthetic compounds for activity against the known efflux pumps of cancer cell types have been screened by the National Cancer Institute (USA) and, to date, not a single inhibitor has found its way toward successful therapy of MDR cancer. In fact, because normal counter type cells have a fully functional efflux pump, albeit at a much lower level of activity, clinical trials with selected efflux pump inhibitors have produced high toxicity and even death.During the past two decades, traditional medicine has become a source for the identification of plants that harbor compounds that may have important potential for the therapy of cancer. With respect to the laboratory of one of the authors of this mini-review (JM), literally, hundreds of plants have been studied for their activity against specific targets of the cancer cell and it is the focus of this mini-review to identify selected compounds that have no toxicity at the level of their in vitro study and which have activity against proliferation or induction of the apoptotic mechanism or the efflux pump responsible for the phenotype of the MDR cancer cell. Targets of MDR Cancer CellsProliferation. Proliferation is affected by many drugs and, although the search for non-toxic compounds that inhibit proliferation was initiated more than 60 years ago, remains the focus of most studies; however, the inhibition of proliferation by compounds isolated from natural sources will not be discussed here at the level of its mechanism. Rather, suffice to say that our observations for antiproliferative activity as presented in the text remain, for the 5665

show abstract

Section: Targets Of Mdr Cancer Cellsmentioning

confidence: 99%

Identification of Important Compounds Isolated from Natural Sources that Have Activity Against Multidrug-resistant Cancer Cell Lines: Effects on Proliferation, Apoptotic Mechanism and the Efflux Pump Responsible for Multi-resistance Phenotype

Amaral

Spengler

Molnár

2016

View full text Add to dashboard Cite

show abstract

“…Effectors that respond to the cellular stress of DNA damage include cyclin-dependent kinase inhibitor 1A (15), growth arrest and DNA-damage-inducible α, p53 dependent G 2 arrest mediator candidate and damage-specific DNA binding protein 2, all of which are regulated by p53 (16,17). Among the 180 genes involved in several repair signaling pathways, numerous genes are regulated by epigenetic mechanisms and are frequently downregulated or silenced in various types of cancer (18 (19)(20)(21)(22)(23)(24)(25).…”

Section: Introductionmentioning

confidence: 99%

Differential expression profile analysis of DNA damage repair genes in CD133+/CD133− colorectal cancer cells

et al. 2017

View full text Add to dashboard Cite

show abstract

“…We refer the reader wishing a more thorough exposition of the biochemistry of DNA repair to a number of excellent recent reviews (13)(14)(15)(16). Instead, we focus on those DNA repair mechanisms and key proteins that have been specifically linked to advanced disease and metastasis, such as DNA damage checkpoint control and TP53, as well as other repair proteins, such as PARP, that are exploitable therapeutically.…”

Section: Introductionmentioning

confidence: 99%

Molecular Pathways: Targeting DNA Repair Pathway Defects Enriched in Metastasis

Corcoran

Clarkson

Stuchbery

et al. 2016

Clinical Cancer Research

View full text Add to dashboard Cite

The maintenance of a pristine genome, free from errors, is necessary to prevent cellular transformation and degeneration. When errors in DNA are detected, DNA damage repair (DDR) genes and their regulators are activated to effect repair. When these DDR pathways are themselves mutated or aberrantly downregulated, cancer and neurodegenerative disorders can ensue. Multiple lines of evidence now indicate, however, that defects in key regulators of DNA repair pathways are highly enriched in human metastasis specimens and hence may be a key step in the acquisition of metastasis and the ability of localized disease to disseminate. Some of the key regulators of checkpoints in the DNA damage response are the TP53 protein and the PARP enzyme family. Targeting of these pathways, especially through PARP inhibition, is now being exploited therapeutically to effect significant clinical responses in subsets of individuals, particularly in patients with ovarian cancer or prostate cancer, including cancers with a marked metastatic burden. Targeting DNA repair-deficient tumors with drugs that take advantage of the fundamental differences between normal repair-proficient cells and repair-deficient tumors offers new avenues for treating advanced disease in the future. Clin Cancer Res; 22(13); 3132-7. Ó2016 AACR.

show abstract

DNA damage response – A double-edged sword in cancer prevention and cancer therapy

Cited by 163 publications

References 72 publications

Identification of Important Compounds Isolated from Natural Sources that Have Activity Against Multidrug-resistant Cancer Cell Lines: Effects on Proliferation, Apoptotic Mechanism and the Efflux Pump Responsible for Multi-resistance Phenotype

Identification of Important Compounds Isolated from Natural Sources that Have Activity Against Multidrug-resistant Cancer Cell Lines: Effects on Proliferation, Apoptotic Mechanism and the Efflux Pump Responsible for Multi-resistance Phenotype

Differential expression profile analysis of DNA damage repair genes in CD133+/CD133− colorectal cancer cells

Molecular Pathways: Targeting DNA Repair Pathway Defects Enriched in Metastasis

Contact Info

Product

Resources

About