The Effect of GADD45a on Furazolidone‐Induced S‐Phase Cell‐Cycle Arrest in Human Hepatoma G2 Cells

Sun, Yu; Tang, Shusheng; Xiao, Xilong

doi:10.1002/jbt.21719

Cited by 14 publications

(9 citation statements)

References 19 publications

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“…As a cell cycle regulator, RB1 controls cell cycle progression and arrests the cell cycle by repressing E2F target genes [ 29 ]. The GADD45A pathway partially influences S-phase cell cycle arrest in G2 cells via cyclin D1, cyclin D3, and CDK6 [ 30 ]. These results suggest that PGL represses cell cycle-related genes and also activates apoptosis-related genes.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome Profiling Reveals the Antitumor Mechanism of Polysaccharide from Marine Algae Gracilariopsis lemaneiformis

Kang

et al. 2016

PLoS ONE

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Seaweed is one of the important biomass producers and possesses active metabolites with potential therapeutic effects against tumors. The red alga Gracilariopsis lemaneiformis (Gp. lemaneiformis) possesses antitumor activity, and the polysaccharide of Gp. lemaneiformis (PGL) has been demonstrated to be an ingredient with marked anticancer activity. However, the anticancer mechanism of PGL remains to be elucidated. In this study, we analyzed the inhibitory effect of PGL on the cell growth of 3 human cancer cell lines and found that PGL inhibited cell proliferation, reduced cell viability, and altered cell morphology in a time- and concentration-dependent manner. Our transcriptome analysis indicates that PGL can regulate the expression of 758 genes, which are involved in apoptosis, the cell cycle, nuclear division, and cell death. Furthermore, we demonstrated that PGL induced apoptosis and cell cycle arrest and modulated the expression of related genes in the A549 cell line. Our work provides a framework to understand the effects of PGL on cancer cells, and can serve as a resource for delineating the antitumor mechanisms of Gp. lemaneiformis.

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Section: Discussionmentioning

confidence: 99%

Transcriptome Profiling Reveals the Antitumor Mechanism of Polysaccharide from Marine Algae Gracilariopsis lemaneiformis

Kang

et al. 2016

PLoS ONE

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“…A new discovery has been found whereby GADD45a influenced furazolidone-induced S-phase cell cycle arrest in HepG2 cells via cyclin D1, cyclin D3, and CDK6 [ 19 ]. GADD45a, a member of GADD45 family, have been implicated in the regulation of many cellular functions, including DNA repair, cell cycle checkpoint, signaling transduction and maintenance of genomic stability [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, after UV irradiation, a pronounced S-phase accumulation of GADD45a deficient cells was observed [ 22 ]. Cyclin A and their relative protein are responsible for regulating the cell cycle transition, some relevant signaling pathways activated when the cell cycle arrest in S-phase, which regulates cell death and inhibition of cell proliferation [ 19 , 24 ]. It suggested that apoptosis in HepG2 cells might be suppressed through p38 MAPK and ROS-phosphorylation of JNK pathways in response to olaquindox treatment [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

GADD45a Regulates Olaquindox-Induced DNA Damage and S-Phase Arrest in Human Hepatoma G2 Cells via JNK/p38 Pathways

Dai

Yang

et al. 2017

Molecules

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Olaquindox, a quinoxaline 1,4-dioxide derivative, is widely used as a feed additive in many countries. The potential genotoxicity of olaquindox, hence, is of concern. However, the proper mechanism of toxicity was unclear. The aim of the present study was to investigate the effect of growth arrest and DNA damage 45 alpha (GADD45a) on olaquindox-induced DNA damage and cell cycle arrest in HepG2 cells. The results showed that olaquindox could induce reactive oxygen species (ROS)-mediated DNA damage and S-phase arrest, where increases of GADD45a, cyclin A, Cdk 2, p21 and p53 protein expression, decrease of cyclin D1 and the activation of phosphorylation-c-Jun N-terminal kinases (p-JNK), phosphorylation-p38 (p-p38) and phosphorylation-extracellular signal-regulated kinases (p-ERK) were involved. However, GADD45a knockdown cells treated with olaquindox could significantly decrease cell viability, exacerbate DNA damage and increase S-phase arrest, associated with the marked activation of p-JNK, p-p38, but not p-ERK. Furthermore, SP600125 and SB203580 aggravated olaquindox-induced DNA damage and S-phase arrest, suppressed the expression of GADD45a. Taken together, these findings revealed that GADD45a played a protective role in olaquindox treatment and JNK/p38 pathways may partly contribute to GADD45a regulated olaquindox-induced DNA damage and S-phase arrest. Our findings increase the understanding on the molecular mechanisms of olaquindox.

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“…In the present study, FZD treatment significantly increased the mRNA level of p53 (Figure 7). Our previous studies had showed that p38 MAPK and GADD45a, a downstream gene of p53, participated in FZD induced cell cycle arrest and apoptosis [51,52]. Another study demonstrated that curcumin protected against 6-hydroxydopamine-induced neurotoxicity through attenuation of p53-mediated apoptosis in the dopaminergic cell line SH-SY5Y [47].…”

Section: Discussionmentioning

confidence: 99%

Curcumin Ameliorates Furazolidone Induced DNA Damage and Apoptosis in Human Hepatocyte L02 Cells via Inhibiting ROS Production and Mitochondrial Pathway

Dai

Gong

et al. 2016

Preprint

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Furazolidone (FZD), a synthetic nitrofuran derivative, has been widely used as an antibacterial and antiprotozoal agent. Recently, the potential toxicity of FZD has raised concerns, but its mechanism is still unclear. This study aimed to investigate the protective effect of curcumin on FZD induced cytotoxicity and the underlying mechanism in human hepatocyte L02 cells. The results showed that curcumin pre-treatment significantly ameliorated FZD induced oxidative stress, characterized by decreased reactive oxygen species (ROS) and malondialdehyde formations, and increased superoxide dismutase, catalase activities and glutathione contents. In addition, curcumin pre-treatment significantly ameliorated the loss of mitochondrial membrane potential, the activation of caspase-9 and -3, and apoptosis caused by FZD. Alkaline comet assay showed that curcumin markedly reduced FZD-induced DNA damage in a dose-dependent manner. Consistently, curcumin pre-treatment markedly down-regulated the mRNA expression levels of p53, Bax, caspase-9 and -3 and up-regulated the mRNA expression level of Bcl-2. Taken together, these results revealed that curcumin protects against FZD induced DNA damage and apoptosis via inhibiting oxidative stress and mitochondrial pathway. Our study indicated that curcumin may be a promising combiner with FZD to reduce FZD-related toxicity in the clinical applications.

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The Effect of GADD45a on Furazolidone‐Induced S‐Phase Cell‐Cycle Arrest in Human Hepatoma G2 Cells

Cited by 14 publications

References 19 publications

Transcriptome Profiling Reveals the Antitumor Mechanism of Polysaccharide from Marine Algae Gracilariopsis lemaneiformis

Transcriptome Profiling Reveals the Antitumor Mechanism of Polysaccharide from Marine Algae Gracilariopsis lemaneiformis

GADD45a Regulates Olaquindox-Induced DNA Damage and S-Phase Arrest in Human Hepatoma G2 Cells via JNK/p38 Pathways

Curcumin Ameliorates Furazolidone Induced DNA Damage and Apoptosis in Human Hepatocyte L02 Cells via Inhibiting ROS Production and Mitochondrial Pathway

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