Preparations of Tripterygium wilfordii, "Thunder God vine", have been used in China to treat
rheumatoid arthritis.
Rheumatoid arthritis, as well as solid
tumors, is closely associated with neovascularization. Antiarthritic drugs therefore may modulate
tumor growth as well as neovascularization. We found that a compound purified from T. wilfordii, the nortriterpenoid,
demethylzeylasteral (TZ-93), inhibited the proliferation of vascular endothelial cells approximately 30 times more effectively than it did for the proliferation of human
tumor cells. In in vitro assays using bovine aortic endothelial cells,
TZ-93 at non-toxic doses inhibited cell migration, expression of
urokinase-type plasminogen activator (uPA)
mRNA and uPA activity. Exogenous addition of uPA restored the inhibitory effect of
TZ-93 on cell migration. In dorsal air-sac assays in BALB/c mice, the
oral administration of 3 mg/kg/day
TZ-93 for 5 days partially inhibited, and 30 mg/kg/day almost completely abrogated, the development of capillary networks induced by human
hepatoblastoma cells. Similarly, 0.3 mg/kg/day
TZ-93 partially inhibited, and 3 or 30 mg/kg/day almost completely blocked, the growth of mouse B16-F10
melanoma cells in a
tumor implantation assay. The highest dose of
TZ-93 significantly reduced the growth of well-vascularized
tumors with volumes of more than 500 mm3.
TZ-93 treatment of
tumor-bearing mice significantly decreased the density of microvessels in the
tumors. We conclude that
TZ-93 may be useful in treating highly vascularized and metastatic
tumors as well as other angiogenic diseases.