Phytochemical Name : Triptolide

Properties Information
PhytoCAT-ID PhytoCAT-82
Phytochemical name or plant extracts Triptolide
PMID 1819894
Literature evidence The results suggest that Tri might have a potential therapeutic effect on some types of solid tumors, e.g., breast and stomach cancers.
IUPAC name (1S,2S,4S,5S,7R,8R,9S,11S,13S)-8-hydroxy-1-methyl-7-propan-2-yl-3,6,10,16-tetraoxaheptacyclo[11.7.0.02,4.02,9.05,7.09,11.014,18]icos-14(18)-en-17-one
Phytochemicals’ class or type of plant extracts Diterpenoid
Source of phytochemicals or plant Extracts Tripterygium wilfordii
Geographical availability China South-Central, China Southeast, Myanmar, Taiwan, Tibet, Vietnam
Plant parts NA
Other cancers Breast cancer, Stomach cancer, Leukemia
Target gene or protein ADAM10, ATM, PARP-1, XRC1, RAD51, miR-146a, Bcl-2 family, RhoA, Rac1, PD-L1, CD206, Arginase 1, CD204, NF-κB, AP-1, MMP9, Notch-1, HES-1, HEY-1, DCLK1, ALDH1, CD133
Gene or Protein evidence Triptolide treatment of MCF-7 breast cancer cells expressing ectopic ADAM10 or dominant negative ADAM10 (DN ADAM10) resulted in a decreased expression of ADAM10 with a concomitant increase in ADAM10 cleaved products. Triptolide reportedly inhibits RNA polymerase II-mediated transcription and ATM activities to interfere with DNA repair. Western blot analysis shows triptolide down-regulated the levels of PARP1 and XRCC1, and slightly decreases the levels of RAD51. miRNAome variation in MDA-MB-231 cells with or without triptolide treatment demonstrated that miR-146a was upregulated following treatment with triptolide. Tritpolide-induced ERK activation modulated the expression of the Bcl-2 protein family member Bax but was not involved in the downregulation of Bcl-xL expression. In addition, following treatment with triptolide, the expression of RhoA and Rac1 was found to be decreased. Triptolide, a natural compound purified from the Chinese herb Tripterygium wilfordii, has been reported to inhibit PD-L1 otherwise known as the B7 homolog 1 (B7-H1) expression in breast cancer. Furthermore, triptolide inhibited the expression of M2 markers, such as CD206, Arginase 1, and CD204, and inhibited the secretion of anti-inflammatory cytokines. The results demonstrated that triptolide decreased the expression of MMP-9 through inhibition of the TPA-induced phosphorylation of extracellular signal-regulated kinase (ERK) and the downregulation of nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) activity. Both celastrol or triptolide reduced Notch -1 activation and expression of its downstream target proteins HES-1 and HEY-1. Furthermore, the compound suppressed expression of cancer stem cell marker proteins DCLK1, ALDH1, and CD133.
Target pathways NF-κB and AP-1 signaling Wnt/β-catenin signaling pathway ERα-mediated signaling pathway p53 pathway PD-1/PD-L1 pathway
IC50 0.504-1.22 μg/L
Potency Triptolide (5-200 nmol/L) dose-dependently inhibited the viability of both MCF-7 and MDA-MB-231 cells, with a more potent inhibition on MCF-7 cells. Triptolide, an extract of Tripterygium wilfordii, has been shown to have a potent anticancer activity. In vitro, TPL inhibited the proliferation and colony formation of tumor cells at extremely low concentrations (2-10 ng/ml) and was more potent than Taxol. Since its isolation from Tripterygium wilfordii in 1972, triptolide has been shown to possess potent anticancer activity against a variety of cancers, and has entered phase I clinical trial.
Cell line/ mice model MCF-7, BT-20,MKN-45, MKN-7, KATO-III, HL-60 , MDA-MB-231, BT-474
Additional information  In addition, Triptolide could also induce interleukin-2 secretion and overcome interleukin-10 inhibition caused by glioma cells under IFN-γ treated condition. In addition, TPL inhibited experimental metastasis of B16F10 cells to the lungs and spleens of mice. In addition, a Transwell assay revealed that triptolide reduced the ability of MCF-7 cells to invade Matrigel.
PubChem ID 107985
Additional PMIDs 25009609 25864647 30563138 1842005 21486687 24043955 31289559 31072418 27609747 18572307 30551406 33924995 31663424 19783906 23467622 25047443 1819894 34093777
Additional sources of information https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:162908-1
Safety Acute toxic in pubmed database.