ArticleLaboratory investigation; a journal of technical methods and pathology2015
Triptolide abrogates growth of colon cancer and induces cell cycle arrest by inhibiting transcriptional activation of E2F.
Article in Laboratory investigation; a journal of technical methods and pathology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- An Updated Insight into the Phytomolecules Reported for the Treatment of Colon Cancer from 2015 to 2024: Systematic Review.Anti-cancer agents in medicinal chemistry · 2026Pooled it
- Triptolide as a multi-target anticancer agent: molecular mechanisms and translational potential.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Triptolide Suppresses Tongue Squamous Cell Carcinoma Progression via PI3K-AKT Pathway Inhibition: An Integrative Network Pharmacology and Experimental Validation Study.The Kaohsiung journal of medical sciences · 2026Article
- Pharmacologic reprogramming of virus-tumor crosstalk enhances measles virus antitumor activity in BRAF mutant colorectal cancer models.Journal of experimental & clinical cancer research : CR · 2026Article
- Multiplexed TrAEL-seq captures DNA replication dynamics in mammalian cells.Nucleic acids research · 2026Article
- Review
- Co‑treatment with triptolide and RSL3 induces hepatocellular carcinoma cell apoptosis and ferroptosis.Molecular medicine reports · 2025Article
- The dual-function of HSP70 in immune response and tumor immunity: from molecular regulation to therapeutic innovations.Frontiers in immunology · 2025Review
- Antitumor mechanisms and future clinical applications of the natural product triptolide.Cancer cell international · 2024Review
- First-in-Human Phase I Study of Minnelide in Patients With Advanced Gastrointestinal Cancers: Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity.The oncologist · 2024Article
- 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
- Nucleo-cytoplasmic shuttling of 14-3-3 epsilon carrying hnRNP C promotes autophagy.Cancer biology & therapy · 2023Article
- Notopterol Suppresses IL-17-Induced Proliferation and Invasion of A549 Lung Adenocarcinoma Cells via Modulation of STAT3, NF-κB, and AP-1 Activation.International journal of molecular sciences · 2023Article
- HSP70 Family in Cancer: Signaling Mechanisms and Therapeutic Advances.Biomolecules · 2023Review
- Triptolide promotes ferroptosis by suppressing Nrf2 to overcome leukemia cell resistance to doxorubicin.Molecular medicine reports · 2023Article
- Identification of Hub Genes for Colorectal Cancer with Liver Metastasis Using miRNA-mRNA Network.Disease markers · 2023Article
- Triptolide promotes degradation of the unfolded gain-of-function Tp53Translational lung cancer research · 2022Article
- Article
- Review
- Identification of potential targets of triptolide in regulating the tumor microenvironment of stomach adenocarcinoma patients using bioinformatics.Bioengineered · 2021Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Despite significant progress in diagnostics and therapeutics, over 50 thousand patients die from colorectal cancer annually. Hence, there is urgent need for new lines of treatment. Triptolide, a natural compound isolated from the Chinese herb Tripterygium wilfordii, is effective against multiple cancers. We have synthesized a water soluble analog of triptolide, named Minnelide, which is currently in phase I trial against pancreatic cancer. The aims of the current study were to evaluate whether triptolide/Minnelide is effective against colorectal cancer and to elucidate the mechanism by which triptolide induces cell death in colorectal cancer. Efficacy of Minnelide was evaluated in subcutaneous xenograft and liver metastasis model of colorectal cancer. For mechanistic studies, colon cancer cell lines HCT116 and HT29 were treated with triptolide and the effect on viability, caspase activation, annexin positivity, lactate dehydrogenase release, and cell cycle progression was evaluated. Effect of triptolide on E2F transcriptional activity, mRNA levels of E2F-dependent genes, E2F1- retinoblastoma protein (Rb) binding, and proteins levels of regulator of G1-S transition was also measured. DNA binding of E2F1 was evaluated by chromatin immunoprecipitation assay. Triptolide decreased colon cancer cell viability in a dose- and time-dependent fashion. Minnelide markedly inhibited the growth of colon cancer in the xenograft and liver metastasis model of colon cancer and more than doubles the median survival of animals with liver metastases from colon cancer. Mechanistically, we demonstrate that at low concentrations triptolide induces apoptotic cell death but at higher concentrations it induces cell cycle arrest. Our data suggest that triptolide is able to induce G1 cell cycle arrest by inhibiting transcriptional activation of E2F1. Our data also show that triptolide downregulates E2F activity by potentially modulating events downstream of DNA binding. Therefore, we conclude that Triptolide and Minnelide are effective against colon cancer in multiple pre-clinical models.
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Registered trials
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.