Arsenic trioxide suppresses transcription of hTERT through down-regulation of multiple transcription factors in HL-60 leukemia cells

Zhang, Yao; Sun, Miao; Shi, Weiwei; Yang, Qingling; Chen, Changjie; Wang, Zhiwei; Zhou, Xin

doi:10.1016/j.toxlet.2014.11.028

Cited by 30 publications

(19 citation statements)

References 29 publications

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“…As the purple fluorescence is an indicator of the location of the p65 protein into the nuclei, this finding suggested that p65 nuclear translocation was enhanced by ATO in HepG2 cells. Our data were consistent with those of previous studies (Ouyang et al, 2006;Wang et al, 2013c), but some reports showed that ATO can inhibit NF-κB in several cell models (Zhang et al, 2014). This discrepancy may be attributed to the different cell lines and model systems used.…”

Section: An Inhibited Ato-induced Activation Of Nf-κb and Its Downstsupporting

confidence: 91%

The role of NF-κB in PARP-inhibitor-mediated sensitization and detoxification of arsenic trioxide in hepatocellular carcinoma cells

et al. 2015

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-The therapeutic efficacy of arsenic trioxide (ATO) for treatments of solid tumors is restricted by its drug resistance and chemotoxicity. In this study, we investigated ATO sensitization and detoxification effect of the Poly (ADP ribose) polymerase-1 (PARP-1) inhibitor 4-Amino-1,8-naphthalimide (4AN) in the hepatocellular carcinoma cell line HepG2. We firstly reported that ATO treatment induced the activation of Nuclear factor of κB (NF-κB) and its downstream anti-apoptosis and pro-inflammatory effectors in a PARP-1-dependent manner and thus conferred HepG2 cells with ATO resistance and toxicity. 4AN significantly suppressed the ATO-induced NF-κB activation, which promotes the apoptotic response and alleviates the inflammatory reaction induced by ATO, resulting in sensitization and detoxification against ATO. We also demonstrated that the ATO-induced activation of PARP-1 and NF-κB was closely associated with the oxidative DNA damage mediated by the generated reactive oxygen species (ROS). Furthermore, the attenuation of ATO-induced ROS and the resulting oxidative DNA damage by N-acetyl-L-cysteine (NAC), a potent antioxidant, significantly reduced the activation of PARP-1 and NF-κB in ATO-treated cells. Our study provides novel insights into the mechanism of the PARP-1-mediated NF-κB signaling pathway in ATO resistance and toxicity in anticancer treatments. This study also highlights the application potential of PARP-1 inhibitors in ATO-based anti-cancer treatments and in prevention of NF-κB-mediated therapeutic resistance and toxicity.

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Section: An Inhibited Ato-induced Activation Of Nf-κb and Its Downstsupporting

confidence: 91%

The role of NF-κB in PARP-inhibitor-mediated sensitization and detoxification of arsenic trioxide in hepatocellular carcinoma cells

et al. 2015

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“…2), the methyl ester of 2-cyano-3,12-dioxo-oleana-1,9-dien-28-oic acid (CDDO-Me) and betulinic acid (a naturally occurring pentacyclic triterpenoid) down-regulate Sp1, Sp3, and Sp4 transcription factors and Spregulated genes (Chintharlapalli, et al, 2011b;Chintharlapalli, et al, 2007;Jutooru, et al, 2010a;Jutooru, et al, 2010c;Jutooru, et al, 2014;Safe, et al, 2014). Arsenic trioxide appears to modulate several pathways in cancer cells leading to increased apoptosis, inhibition of cell proliferation and angiogenesis in cancer cell lines (Jutooru, et al, 2010c;Safe, et al, 2014), and it has been indicated that arsenic trioxide suppresses transcription of the human telomerase reverse transcriptase (hTERT) gene through the regulation of multiple transcription factors, including Sp1 (Zhang, et al, 2015).…”

Section: Drugs and Natural Molecules Which Alter Sp Protein Factors Amentioning

confidence: 99%

Sp1 transcription factor: A long-standing target in cancer chemotherapy

Vizcaíno

Mansilla

Portugal

2015

Pharmacology & Therapeutics

330

244

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“…Gastrokine 1 (GKN1) was reported to inhibit hTERT expression in gastric cancer cells by binding directly to c-Myc and downregulating its expression, leading to lower hTERT promoter activity [207]. The compound arsenic trioxide (ATO) was previously shown to downregulate telomerase activity and this was recently shown to involve the downregulation of four transcription activators of hTERT , one of which is c-Myc [101]. Knockdown of c-Myc (or the other factors) via siRNA could sensitize promyelocytic leukemia cells to ATO-induced apoptosis and inhibition of cell growth.…”

Section: Trans-acting Regulators Of Htert Transcriptionmentioning

confidence: 99%

“…The plant-derived molecule, curcumin, and the drug, pelitinib, were both shown to potently inhibit NF-κB-induced hTERT activation by ionizing radiation in neurogenic cancer and tongue squamous cell carcinoma cells, respectively [148,153]. In addition, arsenic trioxide (ATO) was found to repress the expression of NF-κB (and other transcription factors namely Sp1, c-Myc and Upstream Transcription Factor 2 (USF2)) in human promyelocytic leukemia cells and reduce the transcription of hTERT [101]. …”

Section: Trans-acting Regulators Of Htert Transcriptionmentioning

confidence: 99%

Transcription Regulation of the Human Telomerase Reverse Transcriptase (hTERT) Gene

Ramlee

Wang

Toh

et al. 2016

Genes

132

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Embryonic stem cells and induced pluripotent stem cells have the ability to maintain their telomere length via expression of an enzymatic complex called telomerase. Similarly, more than 85%–90% of cancer cells are found to upregulate the expression of telomerase, conferring them with the potential to proliferate indefinitely. Telomerase Reverse Transcriptase (TERT), the catalytic subunit of telomerase holoenzyme, is the rate-limiting factor in reconstituting telomerase activity in vivo. To date, the expression and function of the human Telomerase Reverse Transcriptase (hTERT) gene are known to be regulated at various molecular levels (including genetic, mRNA, protein and subcellular localization) by a number of diverse factors. Among these means of regulation, transcription modulation is the most important, as evident in its tight regulation in cancer cell survival as well as pluripotent stem cell maintenance and differentiation. Here, we discuss how hTERT gene transcription is regulated, mainly focusing on the contribution of trans-acting factors such as transcription factors and epigenetic modifiers, as well as genetic alterations in hTERT proximal promoter.

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Arsenic trioxide suppresses transcription of hTERT through down-regulation of multiple transcription factors in HL-60 leukemia cells

Cited by 30 publications

References 29 publications

The role of NF-κB in PARP-inhibitor-mediated sensitization and detoxification of arsenic trioxide in hepatocellular carcinoma cells

The role of NF-κB in PARP-inhibitor-mediated sensitization and detoxification of arsenic trioxide in hepatocellular carcinoma cells

Sp1 transcription factor: A long-standing target in cancer chemotherapy

Transcription Regulation of the Human Telomerase Reverse Transcriptase (hTERT) Gene

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