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.
Dat
Nguyen Tien
NT
Center for Molecular Cancer Research, Korean Research Institute of Biosciences and Biotechnology, 685-1 Ochang, Chungbuk 363-883, Korea.
Jin
Xuejun
X
Hong
Young-Soo
YS
Lee
Jung Joon
JJ
D015153:Blotting, Western; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007723:Korea; D015394:Molecular Structure; D016328:NF-kappa B / Q000378:metabolism*; D010946:Plants, Medicinal / Q000737:chemistry*; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D029778:Trichosanthes / Q000737:chemistry*; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology
C550949:4',6-dihydroxy-4-methoxyisoaurone; D051793:Hypoxia-Inducible Factor 1; D016328:NF-kappa B; D012717:Sesquiterpenes; D014315:Triterpenes; C041246:cucurbitacin B