The transcriptional factors nuclear factor-κB (NF-κB) and
NF-E2-related factor 2 (Nrf2) have been recently reported to have critical roles in protecting various tissues against
inflammation and
colitis-associated colorectal cancer (
aberrant crypt foci). Our previous studies showed that
wogonin (5,7-dihydroxy-8-methoxyflavone) possessed anti-neoplastic and anti-inflammatory activities. The present study extended these important earlier findings by exploring the effect of
wogonin on the initiation and development of
colitis-associated cancer.
Wogonin lowered
tumor incidence and inhibited the development of colorectal
adenomas in
azoxymethane- or
dextran sulfate sodium-induced mice. We found that
wogonin significantly decreased the secretion and expression of
IL-6 and IL-1β, reduced cell proliferation and nuclear expression of NF-κB in
adenomas and surrounding tissues and promoted Nrf2 nuclear translocation in surrounding tissues, although overexpressed Nrf2 in
tumor tissues was independent of
wogonin administration. Furthermore,
wogonin inhibited the interaction between human monocytic THP-1 cells and human
colon cancer HCT116 cells, and significantly downregulated
lipopolysaccharide-induced secretion of prototypical pro-inflammatory
cytokines IL-6 and IL-1β in THP-1 cells. Further mechanism research revealed that
wogonin inhibited the nuclear translocation of NF-κB and phosphorylation of IκB and IKKα/β, and promoted Nrf2 signaling pathway in HCT116 cells and THP-1 cells. Taken together, the present results indicated that
wogonin effectively suppressed
inflammation-associated colon
carcinogenesis and
cancer development, suggesting its potential as a chemopreventive agent against
colitis-associated colon cancer.