An isoaurone and other constituents from Trichosanthes kirilowii seeds inhibit hypoxia-inducible factor-1 and nuclear factor-kappaB

Hypoxia-inducible factor-1 and nuclear factor-kappaB have become important targets in Cancer treatment due to their critical role in the regulation of genes involved in tumorigenesis. Bioassay-guided fractionation of the methanol extract of Trichosanthes kirilowii seeds led to the isolation of a naturally rare isoaurone, 4',6-dihydroxy-4-methoxyisoaurone (1), together with three known compounds, cucurbitacin B (2), 6-(3-hydroxy-4-methoxystyryl)-4-methoxy-2H-pyran-2-one (3), and blumenol A (4). All compounds inhibited HIF-1 and NF-kappaB activities in reporter assays. Compounds 1-3 potently inhibited HIF-1alpha accumulation and VEGF secretion under hypoxic condition. These results suggest that the tumor cell growth inhibitory activity of T. kirilowii is likely associated with the inhibition of HIF-1 and NF-kappaB activities.