Inflexinol inhibits colon cancer cell growth through inhibition of nuclear factor-kappaB activity via direct interaction with p50.
Kaurane diterpene compounds have been known to be cytotoxic against several cancer cells through inhibition of nuclear factor-kappaB (NF-kappaB) activity. Here, we showed that inflexinol, a novel kaurane diterpene compound, inhibited the activity of NF-kappaB 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-kappaB 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-kappaB. These results suggest that inflexinol inhibits colon cancer cell growth via induction of apoptotic cell death through inactivation of NF-kappaB by a direct modification of cysteine residue in the p50 subunit of NF-kappaB.
Ban
Jung Ok
JO
College of Pharmacy, Chungbuk National University, 48 Gaeshin-dong, Heungduk-gu, Cheonju, Korea.
Oh
Ju Hoon
JH
Hwang
Bang Yeon
BY
Moon
Dong Cheul
DC
Jeong
Heon-Sang
HS
Lee
Seram
S
Kim
Soyoun
S
Lee
Hyosung
H
Kim
Kyung-Bo
KB
Han
Sang Bae
SB
Hong
Jin Tae
JT
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045786:Diterpenes, Kaurane / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D024202:Electrophoretic Mobility Shift Assay; D045325:HCT116 Cells; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011485:Protein Binding; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D045786:Diterpenes, Kaurane; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D019253:Proto-Oncogene Proteins c-bcl-2; C530049:ent-1,3,6,11-tetrahydroxykaur-16-ene-15-one 3,11-diacetate; D052247:Nitric Oxide Synthase Type II; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D053453:Caspase 9