Triptonide inhibits the pathological functions of gastric cancer-associated fibroblasts

Wang, Zhenfei; Ma, Da-Guang; Wang, Changshan; Zhu, Zhe; Yang, Yong-Yan; Zeng, Fenfang; Yuan, Jiangzi; Liu, Xia; Gao, Yue; Chen, Yongxia; Jia, Yongsheng

doi:10.1016/j.biopha.2017.10.046

Cited by 21 publications

(10 citation statements)

References 39 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%

“…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: Introductionmentioning

confidence: 99%

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

et al. 2019

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“…The current study found that TN could decrease the proliferation, migration, invasion rates and AEG-1 expression, and that overexpressed AEG-1 demonstrated its carcinogenesis, which resulted in increased proliferation, migration and invasion of the tumor cells and the (9). Furthermore, Wang et al observed that the abilities of migration and invasion of gastric cancer-associated fibroblasts (GCAFs) could be greatly inhibited by TN (10). Thus, TN could be explored to inhibit the progression of cancers, including thyroid cancer.…”

Section: Discussionmentioning

confidence: 69%

Triptonide inhibits metastasis potential of thyroid cancer cells via astrocyte elevated gene-1

Fu¹,

Niu²,

Jin³

et al. 2020

Transl Cancer Res TCR

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Background: Triptonide (TN) was recently proved to have anti-tumor effects. The current study explored whether TN inhibited thyroid cancer and the possible underlying mechanism.Methods: MDA-T68 and BCPAP cells were treated by TN. Cell viability, migration and invasion rate were detected by MTT and Transwell. Protein expressions were determined by Western blot and mRNA expressions were detected by Real-time Quantitative PCR (qPCR).Results: TN at the concentration higher than 50 nmol/L inhibited cell viability, migration and invasion of MDA-T68 and BCPAP cells, and astrocyte elevated gene (AEG-1) expression, was decreased by TN at the concentration higher than 50 nmol/L. Furthermore, AEG-1 overexpression inhibited cell viability, migration and invasion capacity of MDA-T68 and BCPAP cells, while TN reduced AEG-1 expression, and weaken the effect of AEG-1 overexpression on cell viability, migration and invasion capacities. Moreover, TN depressed the increase of matrix metalloproteinase (MMP) 2, MMP9 and N-cadherin expressions caused by AEG-1 overexpression. Meanwhile, E-cadherin expression reduced by AEG-1 overexpression was increased by TN.Conclusions: TN could inhibit the metastasis potential of thyroid cancer cells through inhibiting the expression of AEG-1. Our findings reveal the mechanism of TN in the treatment of thyroid cancer, which should be further explored in the study of thyroid cancer.

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“…However, several promising potential therapy targets exist in the form of using neutralizing antibodies, JAK2/STAT3 pathway-specific inhibitors, and silencing the expression of pre-cancerous interleukins secreted by CAFs in the tumor microenvironment. Some other options currently discussed include tranilast, which inhibits the TGF-β/Smad pathway and hence EMT, and triptonide, which promotes the production and secretion of tissue inhibitor of metalloproteinase 2 [127,128]. There is a need for further exploration of their role in GC treatment.…”

Section: Cafs and Signaling Pathwaysmentioning

confidence: 99%

Immunological Aspects of the Tumor Microenvironment and Epithelial-Mesenchymal Transition in Gastric Carcinogenesis

Baj

Brzozowska

Forma

et al. 2020

IJMS

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Infection with Helicobacter pylori, a Gram-negative, microaerophilic pathogen often results in gastric cancer in a subset of affected individuals. This explains why H. pylori is the only bacterium classified as a class I carcinogen by the World Health Organization. Several studies have pinpointed mechanisms by which H. pylori alters signaling pathways in the host cell to cause diseases. In this article, the authors have reviewed 234 studies conducted over a span of 18 years (2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015)(2016)(2017)(2018)(2019)(2020). The studies investigated the various mechanisms associated with gastric cancer induction. For the past 1.5 years, researchers have discovered new mechanisms contributing to gastric cancer linked to H. pylori etiology. Alongside alteration of the host signaling pathways using oncogenic CagA pathways, H. pylori induce DNA damage in the host and alter the methylation of DNA as a means of perturbing downstream signaling. Also, with H. pylori, several pathways in the host cell are activated, resulting in epithelial-to-mesenchymal transition (EMT), together with the induction of cell proliferation and survival. Studies have shown that H. pylori enhances gastric carcinogenesis via a multifactorial approach. What is intriguing is that most of the targeted mechanisms and pathways appear common with various forms of cancer.EMT refers to the process by which the mesenchymal phenotype is acquired by epithelial cells (ECs) mainly via the reduction of their intracellular adhesions and proliferative capacity (Figure 1.) [47].

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Triptonide inhibits the pathological functions of gastric cancer-associated fibroblasts

Cited by 21 publications

References 39 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

Triptonide inhibits metastasis potential of thyroid cancer cells via astrocyte elevated gene-1

Immunological Aspects of the Tumor Microenvironment and Epithelial-Mesenchymal Transition in Gastric Carcinogenesis

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