Natural compounds and their derivatives are an important source of anti-cancer agents.
The tree fern Metaxya rostrata C.Presl (Metaxyaceae) is widespread in the rainforests of Central and South America,
where suspensions of the dried rhizome in water are orally administered against intestinal
ulcers or tumors. An activity-guided study led to the isolation of structurally related
xanthones. Two of them, 2-deprenyl-rheediaxanthone B (XB) and 2-deprenyl-7-hydroxy-rheediaxanthone
B (OH-XB) were analysed and showed cytotoxic activity at concentrations < 10 µM. Both
induced active cell death by distinct mechanisms [1]. Our study detected suppression of the transcription factor FoxM1 as the common
target. Protein as well as mRNA levels were decreased after treatment with both xanthones.
Knockdown of FoxM1 by siRNA interference decreased the cytotoxic effect and xanthone-induced
caspase activity in SW480 colorectal cancer cells. Comparison with additional cell
lines (HCT116, Caco-2, HT29 and DLD1) demonstrated decreased FoxM1 mRNA and protein
levels as well as induction of caspase activity in all except HT29. HT29 cells contained
no detectable FoxM1 protein and were insensitive to both, XB and OH-XB. There was
no difference in the baseline FoxM1 mRNA level between HT29 and the other cell lines.
Therefore, ongoing experiments explore differences in FoxM1 protein stability in compound-exposed
and control cultures.
