Inhibition of RNA polymerase III transcription by Triptolide attenuates colorectal tumorigenesis

Liang, Xuefang; Xie, Renxiang; Su, Jinfeng; Ye, Bingqi; Wei, Saisai; Liang, Ziwen; Bai, Rongpan; Chen, Zhanghui; Li, Zhongxiang; Gao, Xiangwei

doi:10.1186/s13046-019-1232-x

Cited by 35 publications

(24 citation statements)

References 33 publications

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“…The anti-inflammatory mechanism involves inhibition of NF-κB activation and DNA binding of NF-AT to enhancer sites in the IL-2 promoter [115]. Triptolide is a global transcriptional inhibitor of RNAP I, II and III [116][117][118][119], which partly explains its anti-cancer properties. Triptolide inhibits both total RNA and mRNA de novo synthesis in A549 cells.…”

Section: Triptolidementioning

confidence: 99%

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Tat-Based Therapies as an Adjuvant for an HIV-1 Functional Cure

Jin

Lin

et al. 2020

Viruses

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The human immunodeficiency virus type 1 (HIV) establishes a chronic infection that can be well controlled, but not cured, by combined antiretroviral therapy (cART). Interventions have been explored to accomplish a functional cure, meaning that a patient remains infected but HIV is undetectable in the blood, with the aim of allowing patients to live without cART. Tat, the viral transactivator of transcription protein, plays a critical role in controlling HIV transcription, latency, and viral rebound following the interruption of cART treatment. Therefore, a logical approach for controlling HIV would be to block Tat. Tackling Tat with inhibitors has been a difficult task, but some recent discoveries hold promise. Two anti-HIV proteins, Nullbasic (a mutant of Tat) and HT1 (a fusion of HEXIM1 and Tat functional domains) inhibit viral transcription by interfering with the interaction of Tat and cellular factors. Two small molecules, didehydro-cortistatin A (dCA) and triptolide, inhibit Tat by different mechanisms: dCA through direct binding and triptolide through enhanced proteasomal degradation. Finally, two Tat-based vaccines under development elicit Tat-neutralizing antibodies. These vaccines have increased the levels of CD4+ cells and reduced viral loads in HIV-infected people, suggesting that the new vaccines are therapeutic. This review summarizes recent developments of anti-Tat agents and how they could contribute to a functional cure for HIV.

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Section: Triptolidementioning

confidence: 99%

“…Triptolide can alter RNAP II promoter occupancy [121]. A recent paper showed that triptolide reduced the formation of TFIIIB, a multi-subunit transcription factor for RNAP III at the promoters of tRNAs and 5S rRNA in colorectal cancer cells [119].…”

Section: Triptolidementioning

confidence: 99%

Tat-Based Therapies as an Adjuvant for an HIV-1 Functional Cure

Jin

Lin

et al. 2020

Viruses

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“…Previous work [35] suggested that triptolide is able to induce G1 cell cycle arrest by inhibiting transcriptional activation of E2F1. Triptolide was found to reduce both tumor number and tumor size in mice carrying mutations to promote growth of adenomatous polyposis coli as well as in mice treated with azoxymethane/dextran sodium sulfate to induce cancer [36]. Triptolide effectively inhibits CRC cell proliferation, colony formation, and organoid growth in vitro, and these effects are associated with down-regulation of target genes transcribed by RNA polymerase III.…”

Section: Discussionmentioning

confidence: 99%

Prediction of triptolide targets in colorectal cancer using network pharmacology and molecular docking

Song¹,

Dai²,

Zhang³

et al. 2020

Preprint

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Network pharmacology is an approach that uses bioinformatics to predict and identify multiple drug targets and interactions in disease. Here, we applied network pharmacology to investigate the potential mechanisms of action of triptolide, an active component in the traditional Chinese medicine Tripterygium wilfordii Hook F, in colorectal cancer (CRC). We first searched public databases for genes and proteins known to be associated with CRC, as well as those predicted to be targets of triptolide, and then used Ingenuity Pathway Analysis (IPA) to identify enriched gene pathways and networks. Networks and pathways that overlapped between CRC-associated proteins and triptolide target proteins were then used to predict candidate protein targets of triptolide in CRC. The following proteins were found to be expressed in both CRC-associated networks and triptolide target networks: JUN, FOS, CASP3, BCL2, IFNG, and VEGFA. Docking studies suggested that triptolide can fit in the binding pocket of the four top candidate triptolide target proteins (CASP3, BCL2, VEGFA and IFNG). The overlapping pathways were activation of neuroinflammation signaling, glucocorticoid receptor signaling, T helper (Th) cell differentiation, Th1/Th2 activation, and colorectal cancer metastasis signaling. These results show that network pharmacology can be used to generate hypotheses about how triptolide exerts therapeutic effects in CRC. Network pharmacology may be a useful method for characterizing multi-target drugs in complex diseases.

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“…Triptolide kills colorectal cancer cells in vitro and inhibits the growth of colorectal xenografts in a mouse model (Wang et al, 2009;Oliveira et al, 2015). Recently, Liang et al tested triptolide in adenomatous polyposis coli (Apc) mutated mice where it effectively inhibited colorectal cancer proliferation (Liang et al, 2019b). Interestingly, they noted that triptolide also reduced Pol III mediated transcription by inhibiting TFIIIB formation at Pol III target genes.…”

Section: Triptolidementioning

confidence: 99%

Transcription and Translation Inhibitors in Cancer Treatment

et al. 2020

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Transcription and translation are fundamental cellular processes that govern the protein production of cells. These processes are generally up regulated in cancer cells, to maintain the enhanced metabolism and proliferative state of these cells. As such cancerous cells can be susceptible to transcription and translation inhibitors. There are numerous druggable proteins involved in transcription and translation which make lucrative targets for cancer drug development. In addition to proteins, recent years have shown that the "undruggable" transcription factors and RNA molecules can also be targeted to hamper the transcription or translation in cancer. In this review, we summarize the properties and function of the transcription and translation inhibitors that have been tested and developed, focusing on the advances of the last 5 years. To complement this, we also discuss some of the recent advances in targeting oncogenes tightly controlling transcription including transcription factors and KRAS. In addition to natural and synthetic compounds, we review DNA and RNA based approaches to develop cancer drugs. Finally, we conclude with the outlook to the future of the development of transcription and translation inhibitors.

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Inhibition of RNA polymerase III transcription by Triptolide attenuates colorectal tumorigenesis

Cited by 35 publications

References 33 publications

Tat-Based Therapies as an Adjuvant for an HIV-1 Functional Cure

Tat-Based Therapies as an Adjuvant for an HIV-1 Functional Cure

Prediction of triptolide targets in colorectal cancer using network pharmacology and molecular docking

Transcription and Translation Inhibitors in Cancer Treatment

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