Triptonide inhibits lung cancer cell tumorigenicity by selectively attenuating the Shh-Gli1 signaling pathway

Zhang, Mengli; Tan, Shijie; Yu, Di; Zhao, Zhe; Zhang, Bin; Zhang, Pan; Lv, Chunping; Zhou, Quansheng; Cao, Zhifei

doi:10.1016/j.taap.2019.01.002

Cited by 31 publications

(24 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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%

See 1 more Smart Citation

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

et al. 2019

View full text Add to dashboard Cite

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.

show abstract

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

View full text Add to dashboard Cite

show abstract

“…Wang et al 22 indicate that TN inhibits human nasopharyngeal carcinoma cell growth via disrupting Lnc-RNA THOR-IGF2BP1 signaling. Zhang et al 11 imply that TN inhibits lung cancer cell tumorigenicity by selectively attenuating the Shh-Gli1 signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

“…7 However, active ingredients such as triptolide and celastrol extracted from tripterygium had shown to possess anti-inflammatory and anti-tumor effects both in in vivo and in vitro. 8,9 Anticancer effect of triptonide (TN), the other diterpene epoxide constituent of Tripterygium wilfordii, was demonstrated in pancreatic, 10 nasopharyngeal, lung 11 and lymphoma cancer. 12 However, until recently, its growth inhibitory effect on osteosarcoma and its underlying molecular mechanism have not uncovered in detail.…”

Section: Introductionmentioning

confidence: 99%

<p>Triptonide Modulates MAPK Signaling Pathways and Exerts Anticancer Effects via ER Stress-Mediated Apoptosis Induction in Human Osteosarcoma Cells</p>

Fang¹,

Jing²,

Rajamanickam³

et al. 2020

CMAR

View full text Add to dashboard Cite

Background: Osteosarcoma (OS) is the most common primary malignancy arise from bone and is one of the causes of cancer-related deaths. Triptonide (TN), a diterpenoid epoxide presented in Tripterygium wilfordii, is shown to possess a broad spectrum of biological properties. Methods: In this study, we investigate the growth inhibitory effect of TN against human OS cells and its underlying molecular mechanism of action. Results: Findings of our in vitro study revealed that TN exhibited a dose-dependent cytotoxic effect in MG63 and U-2OS cells. ROS-mediated cytotoxic effect was achieved in OS cells treated with TN which was reversed upon NAC treatment. Significantly, increased expression of PERK, p-EIF2, GRP78, ATF4 and CHOP in TN-treated OS cells unfolds the molecular mechanism of TN targets ER stress-mediated apoptosis. Modulation of ERK MAPK pathway was also observed as evidenced by the increased phosphorylation of ERK (p-ERK) and p-p38 in TN-treated OS cells. Conclusion: Altogether, the outcome of the study for the first time revealed that TN exhibited its potential chemotherapeutic effects through ROS-mediated ER stress-induced apoptosis via p38 and ERK MAPK signaling pathways.

show abstract

“…1,3,15 TPN acts as a novel potent anticancer drugs with low toxicity. [16][17][18][19] The differences between the chemical structures of TPL and TPN are the substituent groups at C-14 position in which TPL is with C-14-hydroxyl and TPN is with C-14-carbonyl ( Figure 1A and B). The metabolomics study shows that the hydroxyl group at C-14 in the molecular structure of TPL plays an important role in its hepatotoxicity.…”

Section: Introductionmentioning

confidence: 99%

<p>Intravenous Administration of Triptonide Attenuates CFA-Induced Pain Hypersensitivity by Inhibiting DRG AKT Signaling Pathway in Mice</p>

Ling¹,

Ding²,

Dong³

et al. 2020

JPR

View full text Add to dashboard Cite

Background: Currently, medical treatment of inflammatory pain is limited by a lack of safe and effective therapies. Triptonide (TPN), a major component of Tripterygium wilfordii Hook.f. with low toxicity, has been shown to have good anti-inflammatory and neuroprotective effects. The present study aims to investigate the effects of TPN on chronic inflammatory pain. Materials and Methods: Inflammatory pain was induced by intraplantar injection of complete Freund's adjuvant (CFA). TPN's three different doses were intravenously administered to compare the analgesic efficacy: 0.1 mg/kg, 0.5 mg/kg, and 2.0 mg/kg. The foot swelling was quantitated by measuring paw volume. Mechanical allodynia and thermal hyperalgesia were assessed with von Frey filament testing and Hargreaves' test, respectively. Western blots, qRT-PCR and immunofluorescence tests were used to analyze the expression of pAKT, tumor necrosis factor-α (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6). Two AKT inhibitors, AKT inhibitor Ⅳ and MK-2206, were used to examine AKT's effects on pain behavior and cytokines expression. Results: 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. However, these effects were suppressed by treatment with TPN. Furthermore, TPN treatment inhibited CFA-induced increase of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6. Consistent with the in vivo data, TPN inhibited LPS-induced Akt phosphorylation and inflammatory mediator production in ND7/23 cells. Finally, intrathecal treatment with AKT inhibitor Ⅳ or MK-2206, attenuated CFA-induced mechanical allodynia and thermal hyperalgesia, and simultaneously decreased the mRNA expression of TNF-α, IL-1β, and IL-6 in DRG. Conclusion: 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.

show abstract

Triptonide inhibits lung cancer cell tumorigenicity by selectively attenuating the Shh-Gli1 signaling pathway

Cited by 31 publications

References 59 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

<p>Triptonide Modulates MAPK Signaling Pathways and Exerts Anticancer Effects via ER Stress-Mediated Apoptosis Induction in Human Osteosarcoma Cells</p>

<p>Intravenous Administration of Triptonide Attenuates CFA-Induced Pain Hypersensitivity by Inhibiting DRG AKT Signaling Pathway in Mice</p>

Contact Info

Product

Resources

About