PARP and PARG Inhibitors—New Therapeutic Targets in Cancer Treatment

Fauzee, Nilufer Jasmine Selimah; Perucho, Juan; Wang, Yalan

doi:10.1007/s12253-010-9266-6

Cited by 43 publications

(26 citation statements)

References 101 publications

(142 reference statements)

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“…3c, d). This demonstrates diminished activation of NF-κB in PARG-shRNA cells resulting in decreased expression of its dependent genes [35][36][37][38] Silencing PARG Inhibits Metastasis of Colon Carcinoma MMP2 and MMP9 (Fig. 4c, d).…”

Section: Discussionmentioning

confidence: 98%

RNA Interference of PARG Could Inhibit the Metastatic Potency of Colon Carcinoma Cells via PI3-Kinase/Akt Pathway

Qiao-zhuan¹,

Li²,

Wang³

et al. 2012

Cell Physiol Biochem

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Aims: To investigate the role and mechanism of PARG inhibition of metastatic behavior in colonic carcinoma cells. Methods: We examined the effects of PARG protein knockdown by RNA interference on invasion, migration and matrix adhesion of colon carcinoma cell lines in vitro and using a murine in vivo model of liver metastasis. Metastasis related genes were detected using mRNA and protein levels. Moreover, LY294002, an Akt phosphorylation inhibitor, was used to determine whether the suppression of metastatic behavior of colon carcinoma cells was mediated by Akt phosphorylation that was confirmed by EMSA. Pyrrolidine dithiocarbamate (PDTC) was used as a selective NFĸ-B inhibitor to clarify the relationship between PARG, PARP and NF-ĸB. Results: PARG protein was undetectable following specific shRNA transfection; mRNA and protein levels of PARP were significantly decreased. PARG-shRNA cells showed high levels of phosphorylated Akt with decreased expression of NF-ĸB (both total & nuclear), MMP2 and MMP9. However, no additional changes were noted following inhibition of PI3K/Akt pathway by LY294002 in the PARG-shRNA cells; these cells displayed reduced number of liver metastases when characterized in the murine in vivo model. Conclusion: PARG knockdown, concomitant with inhibition of PARP, suppressed the metastatic potency of colon carcinoma cells by activation of PI3K/Akt signaling pathway.

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Section: Discussionmentioning

confidence: 98%

RNA Interference of PARG Could Inhibit the Metastatic Potency of Colon Carcinoma Cells via PI3-Kinase/Akt Pathway

Qiao-zhuan¹,

Li²,

Wang³

et al. 2012

Cell Physiol Biochem

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“…The level of PAR that has been assayed and quantified in this investigation is the result of the interplay of two main gene products involved in PAR metabolism, PARP and PARG (Fauzee et al, 2010;Feng and Koh, 2013). These genes are proposed to be located on chromosome 14 in mouse (Blake et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Dimethylnitrosamine-Induced Reduction in the Level of Poly-ADP-Ribosylation of Histone Proteins of Blood Lymphocytes - a Sensitive and Reliable Biomarker for Early Detection of Cancer

Kma

Sharan²

2014

Asian Pacific Journal of Cancer Prevention

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Poly-ADP-ribosylation (PAR) is a post-translational modification of mainly chromosomal proteins. It is known to be strongly involved in several molecular events, including nucleosome-remodelling and carcinogenesis. In this investigation, it was attempted to evaluate PAR level as a reliable biomarker for early detection of cancer in blood lymphocyte histones. PAR of isolated histone proteins was monitored in normal and dimethylnitrosamine (DMN)-exposed mice tissues using a novel ELISA-based immuno-probe assay developed in our laboratory. An inverse relationship was found between the level of PAR and period of DMN exposure in various histone proteins of blood lymphocytes and spleen cells. With the increase in the DMN exposure period, there was reduction in the PAR level of individual histones in both cases. It was also observed that the decrease in the level of PAR of histones resulted in progressive relaxation of genomic DNA, perhaps triggering activation of genes that are involved in initiation of transformation. The observed effect of carcinogen on the PAR of blood lymphocyte histones provided us with a handy tool for monitoring biochemical or physiological status of individuals exposed to carcinogens without obtaining biopsies of cancerous tissues, which involves several medical and ethical issues. Obtaining blood from any patient and separating blood lymphocytes are routine medical practices involving virtually no medical intervention, post-procedure medical care or trauma to a patient. Moreover, the immuno-probe assay is very simple, sensitive, reliable and cost-effective. Therefore, combined with the ease of preparation of blood lymphocytes and the simplicity of the technique, immuno-probe assay of PAR has the potential to be applied for mass screening of cancer. It appears to be a promising step in the ultimate goal of making cancer detection simple, sensitive and reliable in the near future.

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“…Endothelial Growth Factor-C via the Nuclear Factor-kappa B Signaling Pathway in CT26 Cells Wei-Qiang Wu 1 , Nilufer Jasmine Selimah Fauzee 1 , Ya-Lan Wang 1 * (Rajesh et al, 2006;Fauzee et al, 2010), decrease colon injury (Cuzzocrea et al, 2006), reduce the evolution of experimental periodontitis (Di Paola et al, 2004), and protect ischemic-reperfusion induced myocardial injury (Pálfi et al, 2005).…”

Section: -Aminoisoquinolinone Reduces the Expression Of Vascularmentioning

confidence: 99%

“…NF-kB is a transcription factor that participates in diverse processes such as immunity, inflammation, cell proliferation, apoptosis or embryonal development (Fauzee et al, 2010;Fauzee et al, 2012;Li et al, 2012) Active NF-kB consist of dimeric combination of members of the NF-kB/Rel transcription factor family (Rothwarf and Karin, 1999).…”

Section: -Aminoisoquinolinone Reduces the Expression Of Vascularmentioning

confidence: 99%

5-Aminoisoquinolinone Reduces the Expression of Vascular Endothelial Growth Factor-C via the Nuclear Factor-kappa B Signaling Pathway in CT26 Cells

Fauzee²,

Wang³

2012

Asian Pacific Journal of Cancer Prevention

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Asian Pacific J Cancer Prev, 13, 991-994 IntroductionCancer metastatic dissemination plays a pivotal role in the progression of malignant tumors. Therefore, the principal goal for the treatment of malignant tumors is to prevent tumor proliferation, invasion and metastasis. Tumor lymphangiogenesis is a key factor for the spread of carcinomatous cells and therefore, usually affects the prognosis of patients. Various evidences from recent advances have demonstrated that tumor-induced lymphangiogenesis is an important mechanism promoting lymphatic metastasis (Karpanen et al., 2001;Mandriota et al., 2001;Skobe et al., 2001).PARP-1 is a monomeric, chromatin-bound enzyme, which is abundantly present in eukaryocytes (except yeast) and is activated by DNA single-strand breaks (Isabelle et al., 2010). PARP-1 uses ADP-ribose units from its substrate NAD + to build a polyanionic poly (ADPribose) polymer onto Glu residues on its acceptor proteins including histones, transcription factors and mainly PARP-1 itself and then recruit the repair apparatus to repair the DNA breaks (Diefenbach and Bürkle, 2005; Woo and Threadgill, 2005). 5-AIQ, a highly water soluble inhibitor, is known to inhibit the activation of PARP-1. Inhibition of PARP-1 activation has been found to prevent angiogenesis

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PARP and PARG Inhibitors—New Therapeutic Targets in Cancer Treatment

Cited by 43 publications

References 101 publications

RNA Interference of PARG Could Inhibit the Metastatic Potency of Colon Carcinoma Cells via PI3-Kinase/Akt Pathway

RNA Interference of PARG Could Inhibit the Metastatic Potency of Colon Carcinoma Cells via PI3-Kinase/Akt Pathway

Dimethylnitrosamine-Induced Reduction in the Level of Poly-ADP-Ribosylation of Histone Proteins of Blood Lymphocytes - a Sensitive and Reliable Biomarker for Early Detection of Cancer

5-Aminoisoquinolinone Reduces the Expression of Vascular Endothelial Growth Factor-C via the Nuclear Factor-kappa B Signaling Pathway in CT26 Cells

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