Inflexinol inhibits colon cancer cell growth through inhibition of nuclear factor-κB activity via direct interaction with p50

Kaurane diterpene compounds have been known to be cytotoxic against several cancer cells through inhibition of nuclear factor-kappa B (NF-kappa B) activity. Here, we showed that inflexinol, a novel kaurane diterpene compound, inhibited the activity of NF-kappa B and its target gene expression as well as cancer cell growth through induction of apoptotic cell death in vitro and in vivo. These inhibitory effects on NF-kappa B activity and on cancer cell growth were suppressed by the reducing agents DTT and glutathione and were abrogated in the cells transfected with mutant p50 (C62S). Sol-gel biochip and surface plasmon resonance analysis showed that inflexinol binds to the p50 subunit of NF-kappa B. These results suggest that inflexinol inhibits colon cancer cell growth via induction of apoptotic cell death through inactivation of NF-kappa B by a direct modification of cysteine residue in the p50 subunit of NF-kappa B. [Mol Cancer Ther 2009;8(6):1613-24]