Cell lines

Human ovarian cancer cell lines SKOV3 and A2780

Preparation method

The solubility of this compound in DMSO is >18mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

15 nM, 24-72 h

Applications

In both SKOV3 and A2780 cells, triptolide (50 nM, 72 h) noticeably inhibited ovarian cancer cell proliferation. Triptolide (15 nM) significantly inhibited cell migration 48 h after wounding. Triptolide (15 nM) markedly blocked the invasive capacity of SKOV3 and A2780 cells.

Animal models

Mice xenografted with human ovarian cancer cell lines SKOV3

Dosage form

Oral administration, 0.1, 0.3 or 1 mg/kg/day, daily

Application

Triptolide (1 mg/kg) significantly reduced the number of metastatic nodules by ~80% in mice xenografted with human ovarian cancer cell lines SKOV3.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

Triptolide is the major bioactive constituent extracted from the Chinese herb Tripterygium wilfordii.
Triptolide inhibit the expression of IL-2 in activated T cells and NF-κB mediated transcription activation [1]. Triptolide also can inhibit colony formation and the proliferation of tumor cells at extremely low concentrations.
Triptolide treatment at the concentration of 15 nM inhibited the invasion and migration of ovarian cancer cells SKOV3 and A2780. Triptolide inhibited MMP7 and MMP19 expression with a dose-dependent manner from 0 to 15 nM in ovarian cancer cells. Triptolide also enhanced expression of the E-cadherin in ovarian cancer cell, then, affected the migration and cell invation.[2] Triptolide triggered a CDK7-mediated degradation of RNAPII, including its robust anticancer properties. Triptolide induced Rpb1 decrease with a dose-dependent manner at lowest 100 nM, resulting to a significant RNAPII reduction in SKOV3 cells.[3] Triptolide caused significant decrease of cell viability in a dose-dependent manner with IC50 value of 74.3 nM in RSF (rheumatoid synovial fibroblasts). Triptolide also has inhibition effect on cell proliferation in RSF with IC50= 20.4 nM. Treatment with triptolide (100 nM) for 24 h caused distinctive morphological changes in synovial cells.[4] Triptolide induces apoptotic death of peripheral T cells and T cell hybridomas by increase of DEVD-cleavable caspases activity at 10-100 ng/ml.[5]
Triptolide also inhibited cytokine-induced MMP-3 expression at 125-150nM in primary human synovial fibroblasts, SW1353 cells, and human OA chondro-cytes protecting artilage from aggrecanase- and MMP -driven breakdown.[6]
References:
[1].    Qiu D, Zhao G, Aoki Y, Shi L, Uyei A, Nazarian S, Ng JC, Kao PN: Immunosuppressant PG490 (triptolide) inhibits T-cell interleukin-2 expression at the level of purine-box/nuclear factor of activated T-cells and NF-kappaB transcriptional activation. J Biol Chem 1999, 274(19):13443-13450.
[2].    Zhao H, Yang Z, Wang X, Zhang X, Wang M, Wang Y, Mei Q, Wang Z: Triptolide inhibits ovarian cancer cell invasion by repression of matrix metalloproteinase 7 and 19 and upregulation of E-cadherin. Exp Mol Med 2012, 44(11):633-641.
[3].    Manzo SG, Zhou ZL, Wang YQ, Marinello J, He JX, Li YC, Ding J, Capranico G, Miao ZH: Natural product triptolide mediates cancer cell death by triggering CDK7-dependent degradation of RNA polymerase II. Cancer Res 2012, 72(20):5363-5373.
[4].    Kusunoki N, Yamazaki R, Kitasato H, Beppu M, Aoki H, Kawai S: Triptolide, an active compound identified in a traditional Chinese herb, induces apoptosis of rheumatoid synovial fibroblasts. BMC Pharmacol 2004, 4:2.
[5].    Yang Y, Liu Z, Tolosa E, Yang J, Li L: Triptolide induces apoptotic death of T lymphocyte. Immunopharmacology 1998, 40(2):139-149.
[6].    Liacini A, Sylvester J, Zafarullah M: Triptolide suppresses proinflammatory cytokine-induced matrix metalloproteinase and aggrecanase-1 gene expression in chondrocytes. Biochem Biophys Res Commun 2005, 327(1):320-327.