ArticleOncotarget2016
Triptolide has anticancer and chemosensitization effects by down-regulating Akt activation through the MDM2/REST pathway in human breast cancer.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 47 citations in OpenAlex.
- Triptolide as a multi-target anticancer agent: molecular mechanisms and translational potential.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Anti-Cancer Research Progress of Triptolide: Mechanisms of Action, Structural Modifications, Nanodelivery Systems and Clinical Challenges.Drug design, development and therapy · 2026Review
- Pharmacological, computational, and mechanistic insights into triptolide's role in targeting drug-resistant cancers.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- The Emerging Role of Natural Products in Cancer Treatment.Archives of toxicology · 2024Review
- Antitumor mechanisms and future clinical applications of the natural product triptolide.Cancer cell international · 2024Review
- Triptolide suppresses IL-1β-induced expression of interleukin-8 by inhibiting ROS-Mediated ERK, AP-1, and NF-κB molecules in human gastric cancer AGS cells.Frontiers in oncology · 2024Article
- Article
- Osthole resensitizes CD133Aging · 2020Article
- Exploiting DNA repair defects in triple negative breast cancer to improve cell killing.Therapeutic advances in medical oncology · 2020Article
- Antitumor properties of triptolide: phenotype regulation of macrophage differentiation.Cancer biology & therapy · 2020Article
- Combination of Anti-Cancer Drugs with Molecular Chaperone Inhibitors.International journal of molecular sciences · 2019Review
- FKBP12 is a predictive biomarker for efficacy of anthracycline-based chemotherapy in breast cancer.Cancer chemotherapy and pharmacology · 2019Article
- Inhibition of insulin-like growth factor 1 signaling synergistically enhances the tumor suppressive role of triptolide in triple-negative breast cancer cells.Oncology letters · 2019Article
- Triptolide suppresses the proliferation and induces the apoptosis of nasopharyngeal carcinoma cells via the PI3K/Akt pathway.Oncology letters · 2019Article
- Triptolide enhances the sensitivity of pancreatic cancer PANC-1 cells to gemcitabine by inhibiting TLR4/NF-κB signaling.American journal of translational research · 2019Article
- Triptolide Decreases Cell Proliferation and Induces Cell Death in Triple Negative MDA-MB-231 Breast Cancer Cells.Biomolecules · 2018Article
- In vivo protective effects of chlorogenic acid against triptolide-induced hepatotoxicity and its mechanism.Pharmaceutical biology · 2018Article
- Nogo-B receptor increases the resistance to tamoxifen in estrogen receptor-positive breast cancer cells.Breast cancer research : BCR · 2018Article
- Triptolide induces protective autophagy and apoptosis in human cervical cancer cells by downregulating Akt/mTOR activation.Oncology letters · 2018Article
- Discovery and optimization of cardenolides inhibiting HSF1 activation in human colon HCT-116 cancer cells.Oncotarget · 2018Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Triptolide has been shown to exhibit anticancer activity. However, its mechanism of action is not clearly defined. Herein we report a novel signaling pathway, MDM2/Akt, is involved in the anticancer mechanism of triptolide. We observed that triptolide inhibits MDM2 expression in human breast cancer cells with either wild-type or mutant p53. This MDM2 inhibition resulted in decreased Akt activation. More specifically, triptolide interfered with the interaction between MDM2 and the transcription factor REST to increase expression of the regulatory subunit of PI3-kinase p85 and consequently inhibit Akt activation. We further showed that, regardless of p53 status, triptolide inhibited proliferation, induced apoptosis, and caused G1 phase cell cycle arrest. Triptolide also enhanced the cytotoxic effect of doxorubicin. MDM2 inhibition plays a causative role in these effects. The inhibitory effect of triptolide on MDM2-mediated Akt activation was eliminated with MDM2 overexpression. MDM2-overexpressing tumor cells, in turn, were less susceptible to the anticancer and chemosensitization effects of triptolide than control cells. Triptolide also exhibited anticancer and chemosensitization effects in nude mouse xenograft model. When it was administered to tumor-bearing nude mice, triptolide inhibited tumor growth and enhanced the antitumor effects of doxorubicin. In summary, triptolide has anticancer and chemosensitization effects by down-regulating Akt activation through the MDM2/REST pathway in human breast cancer. Our study helps to elucidate the p53-independent regulatory function of MDM2 in Akt signaling, offering a novel view of the mechanism by which triptolide functions as an anticancer agent.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.