Induction of DNA damage and ATF3 by retigeric acid B, a novel topoisomerase II inhibitor, promotes apoptosis in prostate cancer cells

Liu, Yongqing; Gao, Feng‐Juan; Jiang, Hanming; Niu, Leilei; Bi, Yiling; Young, Charles Y.F.; Yuan, Huipin; Lou, Hongxiang

doi:10.1016/j.canlet.2013.05.022

Cited by 32 publications

(17 citation statements)

References 49 publications

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“…The tumor suppressor role of ATF3 in prostate cancer is also supported by the observations that ATF3 is a proapoptotic molecule in prostate cancer cells and that ATF3 represses androgen receptor signaling required for sustaining the growth and survival of prostate cancer cells 1 , 13 , 14 . However, ATF3 expression was also shown to promote invasion of a human prostate cancer cell line and lung colonization of a rat prostate cancer cell line 22 , 38 .…”

Section: Discussionmentioning

confidence: 83%

“…Although recent studies have revealed that ATF3 contributes to many important human diseases including secondary infections during sepsis-associated immunosuppression 10 and skin cancer induced by immunosuppressants 11 , the role of ATF3 in cancer, particularly prostate cancer, remains poorly understood 12 . Whereas ATF3 appears to be proapoptotic in prostate cancer cells 13 , 14 , ATF3 also binds the androgen receptor (AR) and represses androgen signaling indispensable for sustaining prostate cancer cell proliferation and survival 1 , indicating that ATF3 could be a putative tumor suppressor for prostate cancer. Indeed, several unbiased microarray results have revealed that ATF3 expression is downregulated in prostate cancers, particularly in metastatic prostate cancers 15 , 16 .…”

Section: Introductionmentioning

confidence: 99%

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Loss of ATF3 promotes Akt activation and prostate cancer development in a Pten knockout mouse model

Wang

Ding

et al. 2014

Oncogene

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Activating transcription factor 3 (ATF3) responds to diverse cellular stresses, and regulates oncogenic activities (e.g., proliferation, survival and migration) through direct transcriptional regulation or protein-protein interactions. Although aberrant ATF3 expression is frequently found in human cancers, the role of ATF3 in tumorigenesis is poorly understood. Here we demonstrate that ATF3 suppresses the development of prostate cancer induced by knockout of the tumor suppressor Pten in mouse prostates. Where as the oncogenic stress elicited by Pten loss induced ATF3 expression in prostate epithelium, we found that ATF3 deficiency increased cell proliferation and promoted cell survival, leading to early onset of mouse prostatic intraepithelial neoplasia and the progression of prostate lesions to invasive adenocarcinoma. Importantly, loss of ATF3 promoted activation of the oncogenic AKT signaling evidenced by high levels of phosphorylated AKT and S6 proteins in ATF3-null prostate lesions. In line with these in vivo results, knockdown of ATF3 expression in human prostate cancer cells by sgRNA-mediated targeting activated AKT and increased matrix metalloproteinase-9 expression. Our results thus link ATF3 to the AKT signaling, and suggest that ATF3 is a tumor suppressor for the major subset of prostate cancers harboring dysfunctional Pten.

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Section: Discussionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Loss of ATF3 promotes Akt activation and prostate cancer development in a Pten knockout mouse model

Wang

Ding

et al. 2014

Oncogene

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“…Prolonged treatment with DI generally causes gradual DNA damage, resulting in ATR phosphorylating and activating Chk1, which in turn reduces the level of cdc25c protein 19,20 . In our study, neither p-ATM nor p-ATR was altered with treatment duration (Figure 5B).…”

Section: Discussionmentioning

confidence: 99%

Deacetylisovaltratum disrupts microtubule dynamics and causes G2/M-phase arrest in human gastric cancer cells in vitro

Zhang

Zhou

et al. 2016

Acta Pharmacol Sin

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Aim:Deacetylisovaltratum (DI) is isolated from the traditional Chinese herbal medicine Patrinia heterophylla Bunge, which exhibits anti-cancer activity. Here, we investigated the effects of DI on human gastric carcinoma cell lines in vitro and elucidated its anti-cancer mechanisms.Methods:Human gastric carcinoma AGS and HGC-27 cell lines were treated with DI, and cell viability was detected with MTT assay. Cell cycle stages, apoptosis and mitochondrial membrane potential were measured using flow cytometry. Protein levels were analyzed by Western blotting. Tubulin polymerization assays and immunofluorescence were used to characterize the tubulin polymerization process.Results:DI inhibited the cell viability of AGS and HGC-27 cells in a dose- and time-dependent manner with IC50 values of 12.0 and 28.8 μmol/L, respectively, at 24 h of treatment. Treatment with DI (10–100 μmol/L) dose-dependently promoted tubulin polymerization, and induced significant G2/M cell cycle arrest in AGS and HGC-27 cells. Moreover, DI treatment disrupted mitochondrial membrane potential and induced caspase-dependent apoptosis in AGS and HGC-27 cells.Conclusion:DI induces G2/M-phase arrest by disrupting tubulin polymerization in human gastric cancer cells, which highlights its potent anti-cancer activity and potential application in gastric cancer therapy.

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“…ATF3 deficiency-inhibited PI3K/AKT impaired anti-apoptotic functions in mast cells (24). Some studies also showed that ATF3 may be a proapoptotic factor by increasing apoptosis-related genes such as DR5, DDIT4, CDC25A, GADD45A or up-regulating endoplasmic stress in cancer diseases (39)(40)(41). In addition, ATF3 can repress NRF2-regulated stress pathway by ATF3-NRF2 proteinprotein interactions in NmuMG cells (21).…”

Section: Discussionmentioning

confidence: 99%

ATF3-Mediated NRF2/HO-1 Signaling Regulates TLR4 Innate Immune Responses in Mouse Liver Ischemia/Reperfusion Injury

Rao

Qian

et al. 2015

American Journal of Transplantation

117

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Activating transcription factor 3 (ATF3) is a stressinduced transcription factor that has been shown to repress inflammatory gene expression in multiple cell types and diseases. However, little is known about the roles and mechanisms of ATF3 in liver ischemia/ reperfusion injury (IRI). In warm and cold liver IRI models, we showed that ATF3 deficiency significantly increased ischemia/reperfusion (IR)-stressed liver injury, as evidenced by increased serum alanine aminotransferase levels, histological liver damage, and hepatocellular apoptosis. These may correlate with inhibition of the intrahepatic nuclear factor erythroid-derived 2-related factor 2/heme oxygenase-1 (NRF2/HO-1) signaling pathway leading to enhancing Toll-like receptor 4/nuclear factor kappa beta (TLR4/NF-kB) activation, pro-inflammatory programs and macrophage/neutrophil trafficking, while simultaneously repressing antiapoptotic molecules in ischemic liver. Interestingly, activation of NRF2/HO-1 signaling using an NRF2 activator, oltipraz (M2), during hepatic IRI-rescued ATF3 anti-inflammatory functions in ATF3-deficient mice. For in vitro studies, ATF3 ablation in lipopolysaccharide (LPS)-stimulated bone marrow-derived macrophages (BMMs) depressed levels of NRF2/HO-1 and PI3K/AKT, resulting in enhanced TLR4/NF-kB activation. Pretreatment of LPS-stimulated BMMs with M2 increased NRF2/HO-1 expression, promoted PI3K/AKT, which in turn suppressed TLR4/NF-kB-mediated proinflammatory mediators. Thus, our results first demonstrate ATF3-mediated NRF2/HO-1 signaling in the regulation of TLR4-driven inflammatory responses in IR-stressed livers. Our findings provide a rationale for a novel therapeutic strategy for managing IR-induced liver injury.Abbreviations: ATF3, activating transcription factor 3; BMMs, bone marrow-derived macrophages; bZIP, basic leucine zipper; HMGB1, high mobility group box 1; HO-1, heme oxygenase-1; HPF, high power field; IR, ischemia/reperfusion; IRI, ischemia/reperfusion injury; LPS, lipopolysaccharide; MPO, myeloperoxidase; NF-kB, nuclear factor kappa beta; NRF2, nuclear factor erythroid-derived 2-related factor 2; OLT, orthotopic liver transplantation; sALT, serum alanine aminotransferase; TLR4, Toll-like receptor 4; TNF-a, tumor necrosis factor-alpha; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling

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Induction of DNA damage and ATF3 by retigeric acid B, a novel topoisomerase II inhibitor, promotes apoptosis in prostate cancer cells

Cited by 32 publications

References 49 publications

Loss of ATF3 promotes Akt activation and prostate cancer development in a Pten knockout mouse model

Loss of ATF3 promotes Akt activation and prostate cancer development in a Pten knockout mouse model

Deacetylisovaltratum disrupts microtubule dynamics and causes G2/M-phase arrest in human gastric cancer cells in vitro

ATF3-Mediated NRF2/HO-1 Signaling Regulates TLR4 Innate Immune Responses in Mouse Liver Ischemia/Reperfusion Injury

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