The cell death and DNA damages caused by the Tet-On regulating HSV-tk/GCV suicide gene system in MCF-7 cells

Zeng, Zhao-jun; Xiang, Shengguang; Xue, Vivian Weiwen; Li, Hong-De; Ma, Nan; Ren, Zijing; Xu, Zhujun; Jiao, Chun-Hong; Wang, Cui-Yun; Hu, Weixin

doi:10.1016/j.biopha.2014.07.018

Cited by 8 publications

(11 citation statements)

References 13 publications

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“…38 Interestingly, it has been previously shown that cell cycle arrest and a p53-mediated p21 cip1 induction were observed in GCV-treated tumor cells genetically modified to express HSV-TK in vitro. 39 , 40 These results are similar to our findings in this study, although only GCV itself was used here. In our study, we observed an early and significant induction of p53 and p21 cip1 after GCV treatment.…”

Section: Discussionsupporting

confidence: 89%

Antiviral Drug Ganciclovir Is a Potent Inhibitor of the Proliferation of Müller Glia–Derived Progenitors During Zebrafish Retinal Regeneration

Zhang

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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PurposeThe purpose of this study was to investigate the effect of the antiviral drug ganciclovir (GCV) on Müller glia dedifferentiation and proliferation and the underlying cellular and molecular mechanisms in adult zebrafish.MethodsA Tg(1016tuba1a:GFP) transgenic line was generated to identify injury-induced dedifferentiation of Müller glia. Mechanical retinal damage was induced by a needle-poke injury on the back of the eyes in adult zebrafish. Phosphate-buffered saline or GCV was injected into the vitreous of the eye at the time of injury or through the cornea. The GCV clearance rate from the eye was determined by a reversed-phase HPLC method. Green fluorescent protein (GFP) and bromodeoxyuridine (BrdU) immunofluorescence were used to determine the effect of GCV on retinal regeneration. Cell apoptosis was evaluated by TUNEL staining. Microglia were labeled by vitreous injection of isolectin IB4 conjugates. Quantitative (q)PCR and Western blot analysis were used to determine gene expression in the retina.ResultsGanciclovir treatment significantly reduced the number of BrdU+ Müller glia–derived progenitor cells (MGPCs) at 4 days post injury. Further analysis showed that GCV had no impact on Müller glia dedifferentiation and the initial formation of MGPCs. Our data indicate that GCV irreversibly inhibited MGPC proliferation likely through a p53-p21cip1–dependent pathway. Interestingly, unlike control cells, GCV-treated Müller glia cells were “locked” in a prolonged dedifferentiated state.ConclusionsOur study uncovered a novel inhibitory effect of GCV on MGPC proliferation and suggests its potential use as a tool to uncover molecular mechanisms underlying retinal regeneration in zebrafish.

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Section: Discussionsupporting

confidence: 89%

Antiviral Drug Ganciclovir Is a Potent Inhibitor of the Proliferation of Müller Glia–Derived Progenitors During Zebrafish Retinal Regeneration

Zhang

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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“…10 Large numbers of these DNA clouds were detected in most comet studies of buccal samples. 10,14,15 Accordingly, in the present study, these outliers or invalid comets were excluded from the quantitative analysis to avoid overestimating DNA damage.…”

Section: Discussionmentioning

confidence: 99%

Comet Assay Assessment of DNA Damage in Buccal Mucosa Cells Exposed to X-Rays via Panoramic Radiography

Yanuaryska

2018

J Dent Indones

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Ionizing radiation (IR) presents a risk to human health via DNA damage even when administered at low doses, such as those used in panoramic radiography. Objectives: This study used the comet assay to assess DNA damage in buccal mucosa cells consequent to X-ray radiation from panoramic radiography. Methods: Twenty participants were recruited from among patients who underwent panoramic examinations at Prof. Soedomo Dental Hospital, Universitas Gadjah Mada, and divided into two groups of 10. Buccal mucosa cells were collected from all participants before exposure to IR and at 30 min or 24 h after exposure in groups 1 and 2, respectively, and subjected to a comet assay to assess DNA damage. Assay output images were analyzed using OpenComet software. Double-strand breaks (DSBs) were assessed by comparing the percentages of tail DNA in output images obtained before and after X-ray exposure. Results: A statistically significant (p=0.014) increase in the percentage of tail DNA was observed at 30 min after exposure, but not at 24 h (p=0.29). Conclusion: Panoramic X-ray radiation may induce DSBs in human buccal mucosal cells within 30 min after exposure.

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“…The HSV-TK/GCV system is one of the most promising gene therapies for the tumor. After HSV-TK gene was transfected into tumor cells, its encoding product (thymidine kinase) can phosphorylate non-toxic GCV to cytotoxic GCV triphosphate (GCV-TP), which is involved in the DNA replication and leads to an advanced replicate termination with the following apoptosis of cancer cells (Figure 3; Chen et al., 2014; Zeng et al., 2014). As the affinity of GCV to HSV-TK is about 1,000 times higher than that of cell TK, GCV is preferentially phosphorylated by exogenous HSV-TK in TK-positive tumor cells (Osaki et al., 1994); in other words, the HSV-TK/GCV system has little effect on normal tissues while performing its antitumor role.…”

Section: Progress In the Functional Application Of α-Herpesvirus Thymmentioning

confidence: 99%

“…In general, the possible pathways via which the HSV-TK/GCV system induces tumor cell death include apoptotic and nonapoptotic pathways, but the specific mechanism has not yet been fully elucidated (Wei et al., 1998; Tomicic et al., 2002b; Yin et al., 2012; Zeng et al., 2014). The non-apoptotic pathway is primarily involved in the direct cytotoxicity.…”

Section: Progress In the Functional Application Of α-Herpesvirus Thymmentioning

confidence: 99%

Alpha-Herpesvirus Thymidine Kinase Genes Mediate Viral Virulence and Are Potential Therapeutic Targets

Xie

Wang

et al. 2019

Front. Microbiol.

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Alpha-herpesvirus thymidine kinase (TK) genes are virulence-related genes and are nonessential for viral replication; they are often preferred target genes for the construction of gene-deleted attenuated vaccines and genetically engineered vectors for inserting and expressing foreign genes. The enzymes encoded by TK genes are key kinases in the nucleoside salvage pathway and have significant substrate diversity, especially the herpes simplex virus 1 (HSV-1) TK enzyme, which phosphorylates four nucleosides and various nucleoside analogues. Hence, the HSV-1 TK gene is exploited for the treatment of viral infections, as a suicide gene in antitumor therapy, and even for the regulation of stem cell transplantation and treatment of parasitic infection. This review introduces the effects of α-herpesvirus TK genes on viral virulence and infection in the host and classifies and summarizes the current main application domains and potential uses of these genes. In particular, mechanisms of action, clinical limitations, and antiviral and antitumor therapy development strategies are discussed.

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The cell death and DNA damages caused by the Tet-On regulating HSV-tk/GCV suicide gene system in MCF-7 cells

Cited by 8 publications

References 13 publications

Antiviral Drug Ganciclovir Is a Potent Inhibitor of the Proliferation of Müller Glia–Derived Progenitors During Zebrafish Retinal Regeneration

Antiviral Drug Ganciclovir Is a Potent Inhibitor of the Proliferation of Müller Glia–Derived Progenitors During Zebrafish Retinal Regeneration

Comet Assay Assessment of DNA Damage in Buccal Mucosa Cells Exposed to X-Rays via Panoramic Radiography

Alpha-Herpesvirus Thymidine Kinase Genes Mediate Viral Virulence and Are Potential Therapeutic Targets

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