Triptonide inhibits human nasopharyngeal carcinoma cell growth via disrupting Lnc-RNA THOR-IGF2BP1 signaling

Wang, Shusheng; Lv, Yan; Xu, Xinchun; Zuo, Yun; Yu, Shizhu; Wu, Geping; Lu, Pei-Hua; Zhang, Zhiqing; Chen, Min-Bin

doi:10.1016/j.canlet.2018.11.028

Cited by 78 publications

(71 citation statements)

References 37 publications

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“…Previous studies reported that triptonide plays critical roles in suppression of acute myeloid leukemia, lymphoma, gastric cancer, pancreatic cancer, nasopharyngeal carcinomas, and lung cancer . However, its anticancer mechanisms are still not clear.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, the level of the phosphorylation of mTOR downstream regulatory protein p70S6K was also decreased by triptonide treatment in PC3 ( Figure 6C). Previous studies reported that triptonide plays critical roles in suppression of acute myeloid leukemia, 7 lymphoma, 8 gastric cancer, 9 pancreatic cancer, 10 nasopharyngeal carcinomas, 11 and lung cancer. 12 However, its anticancer mechanisms are still not clear.…”

Section: Triptonide Inhibits the Mtor Signaling Pathwaymentioning

confidence: 99%

“…The latest studies reported that triptonide has a good effect on the suppression of cancers. [7][8][9][10][11][12] Triptonide can induce leukemic cell aging and achieve the antileukemia effects at a very low dose, 7 inhibits transcription of proto-oncogene Lyn in lymphoma, 8 inhibits the pathological progression in gastric cancer related to fibroblasts, 9 inhibits pancreatic cancer cell growth-mediated vasculogenic mimicry by inhibiting VE-cadherin and chemokine ligand 2 gene, 10 inhibits human nasopharyngeal carcinoma cell growth via disrupting long noncoding RNA (lnc-RNA) THOR-IGF2BP1 signaling, 11 and also inhibits lung cancer cell tumorigenicity by selectively attenuating the Shh-Gli1 signaling pathway. 12 The above functions remind us that triptonide act as a broad-spectrum anticancer drug.…”

Section: Introductionmentioning

confidence: 99%

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Triptonide acts as a novel antiprostate cancer agent mainly through inhibition of mTOR signaling pathway

et al. 2019

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Background The increasing incidence of prostate cancer (PCa) indicates an urgent need for the development of new effective drugs in PCa therapy. Triptonide has been reported to have a strong inhibition activity in cancers through screening of Chinese herbal medicine. This study aims to investigate the effects of triptonide on anti‐PCa activity and its mechanisms. Methods Three human advanced PCa cell lines PC3, DU145, and LNCap, and a human normal prostate epithelial cell line RWPE were treated with a range (0, 1.25, 2.5, 5, 10, 20, 40, 80, 160, and 320 nM) of triptonide concentrations for 72 hours respectively. Then, cell viability was assessed by cell counting kit‐8. PCa cells were treated with different doses (0‐20 nM) of triptonide for 72 hours. Cell cycle and apoptosis were assessed by flow cytometry assays. Nude mice bearing human PCa xenografts were intraperitoneally injected daily with either triptonide (10 mg/kg/d) or phosphate‐buffered saline as a control for 35 days. RNA‐sequencing (RNA‐seq) was performed by an Illumina Hiseq Sequencing platform and confirmed by a real‐time polymerase chain reaction. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway analysis, and ingenuity pathway analysis were used to analyze RNA‐seq results. Results Triptonide effectively inhibits the proliferation of human PCa cells PC3, DU145, and LNCap in vitro with their IC50 values as 11.961, 10.259, and 12.012 nM, respectively. Triptonide (10 mg/kg) potently inhibits the growth of PCa cell xenografts in vivo at an inhibition rate of over 97.95%. Treatment with triptonide (5 nM) significantly promotes cell apoptosis and retaining cell‐cycle arrest in the G2/M phase. RNA‐seq data revealed that total of 936 genes were upregulated or downregulated in triptonide treated. Moreover, the phosphorylation of mechanistic target of rapamycin (mTOR) and the downstream protein p70S6K were both inhibited, most obviously in PCa cells. Conclusions Our findings suggest that triptonide can efficaciously suppress PCa growth in vitro and in vivo via inhibiting the phosphorylation of mTOR and the activities of related downstream signaling pathways.

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Section: Discussionmentioning

confidence: 99%

Section: Triptonide Inhibits the Mtor Signaling Pathwaymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Triptonide acts as a novel antiprostate cancer agent mainly through inhibition of mTOR signaling pathway

et al. 2019

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“…RNA extraction and quantitative real time-PCR assay (qPCR, using the ABI Prism 7500 Fast Real-Time PCR system) were performed as described 21 . The melt curve analysis was applied to calculate product melting temperature.…”

Section: Methodsmentioning

confidence: 99%

LIN28B-AS1-IGF2BP1 binding promotes hepatocellular carcinoma cell progression

Zhang

Yang

et al. 2020

Cell Death Dis

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IGF2BP1 overexpression promotes hepatocellular carcinoma (HCC) progression. Long non-coding RNA LIN28B-AS1 directly binds to IGF2BP1. In the present study, LIN28B-AS1 and IGF2BP1 expression and their potential functions in HCC cells were tested. Genetic strategies were applied to interfere their expression, and cell survival, proliferation and apoptosis were analyzed. We show that LIN28B-AS1 is expressed in established/primary human HCC cells and HCC tissues. RNA-immunoprecipitation (RIP) and RNA pull-down results confirmed that LIN28B-AS1 directly associated with IGF2BP1 protein in HCC cells. LIN28B-AS1 silencing (by targeted siRNAs) or knockout (KO, by CRISPR-Cas9 method) depleted IGF2BP1-dependent mRNAs (IGF2, Gli1, and Myc), inhibiting HCC cell growth, proliferation, migration, and invasion. Conversely, ectopic overexpression of LIN28B-AS1 upregulated IGF2BP1-dependent mRNAs and promoted HCC cell progression in vitro. Importantly, ectopic IGF2BP1 overexpression failed to rescue LIN28B-AS1-KO HepG2 cells. LIN28B-AS1 siRNA and overexpression were ineffective in IGF2BP1-KO HepG2 cells. In vivo, LIN28B-AS1 KO-HepG2 xenograft tumors grew significantly slower than the control tumors in the nude mice. Taken together, we conclude that LIN28B-AS1 associates with IGF2BP1 to promote human HCC cell progression in vitro and in vivo.

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“…The metabolomics study shows that the hydroxyl group at C-14 in the molecular structure of TPL plays an important role in its hepatotoxicity [14,15]. TPN acts as a novel potent anticancer drugs with low toxicity [16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Intravenous administration of triptonide attenuates CFA-induced pain hypersensitivity through inhibiting AKT signaling pathway in mice

Ling

Ding

Gao

et al. 2020

Preprint

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Background: Triptonide (TPN) is a major component of Tripterygium wilfordii Hook.f., and reportedly has anti-inflammatory and neuroprotective effects. Recent studies have demonstrated that the phosphatidylinositol 3-kinase (PI3K)/AKT pathway plays an important role in the pathogenesis of inflammatory pain. Here we investigated the anti-nociceptive effect of systemic treatment with TPN on mouse models of chronic inflammatory pain and explored possible mechanisms. Results: Unilateral hind paw injection of complete Freund’s adjuvant (CFA) induced paw edema and persistent pain hypersensitivity. Intravenous treatment with TPN attenuated CFA-induced paw edema, mechanical allodynia, and thermal hyperalgesia. Western blotting and immunofluorescence results showed that CFA induced AKT activation in the dorsal root ganglion (DRG) neurons, which was inhibited by TPN treatment. Furthermore, TPN treatment inhibited mRNA increase of proinflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin 1 beta (IL-1β), and Interleukin 6 (IL-6)] induced by CFA. Finally, pretreatment with AKT inhibitor, AKT inhibitor Ⅳ, attenuated CFA-induced mechanical allodynia and thermal hyperalgesia, and decreased the mRNA expression of pro-inflammatory cytokines. Conclusions: These data indicate that TPN attenuates CFA-induced pain potentially via inhibiting AKT-mediated pro-inflammatory cytokines production in DRG. TPN may be used for the treatment of chronic inflammatory pain.

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Triptonide inhibits human nasopharyngeal carcinoma cell growth via disrupting Lnc-RNA THOR-IGF2BP1 signaling

Cited by 78 publications

References 37 publications

Triptonide acts as a novel antiprostate cancer agent mainly through inhibition of mTOR signaling pathway

Triptonide acts as a novel antiprostate cancer agent mainly through inhibition of mTOR signaling pathway

LIN28B-AS1-IGF2BP1 binding promotes hepatocellular carcinoma cell progression

Intravenous administration of triptonide attenuates CFA-induced pain hypersensitivity through inhibiting AKT signaling pathway in mice

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