Inotilone suppresses phorbol ester-induced inflammation and tumor promotion in mouse skin.
METHODS
Chemoprevention is one of the most feasible approaches to reduce the risk of cancer. Over the past decades, scientists have realized that chronic inflammation is a critical component of cancer development. Inotilone, existing in Inonotus mushroom has been reported to exhibit anti-inflammatory properties in vitro. Hence, we investigated the effects of inotilone on 12-O-tetradecanoylphorbol-13-acetate (TPA)-mediated acute inflammation and tumor promotion in mouse skin and the underlying molecular mechanisms.


RESULTS
Inotilone was topically applied to mouse skin 30 min prior to TPA treatment. The results have shown that inotilone inhibited the production of inflammatory mediators by attenuating the activation of nuclear factor-κB (NF-κB) and the expression of CCAAT/enhancer binding protein β (C/EBPβ). Furthermore, the ability of inotilone to prevent tumorigenesis at promotion stage was evaluated using a classical two-stage mouse skin carcinogenesis model. After initiation of 7,12-dimethylbenz[a]anthracene (DMBA), applying inotilone topically before each TPA treatment was found to reduce the tumor incidence and tumor multiplicity of papillomas.


CONCLUSIONS
Based on the results, we concluded that inotilone has potential to be developed into an effective chemopreventive agent for the treatment of a variety of inflammatory diseases, especially the prevention and treatment of epithelial skin cancer.
Department of Food Science, Rutgers University, New Brunswick, NJ, USA.
Yu-Ching
YC
Kuo
Ching-Shu
CS
Lai
Chen-Yu
CY
Tsai
Kalyanam
K
Nagabhushanam
Chi-Tang
CT
Ho
Min-Hsiung
MH
Pan
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D002273:Carcinogens / Q000633:toxicity; D051546:Cyclooxygenase 2 / Q000378:metabolism; D003872:Dermatitis / Q000188:drug therapy*; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005663:Furans / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism; D018942:Macrolides / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012878:Skin Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity
D000893:Anti-Inflammatory Agents; D022782:CCAAT-Enhancer-Binding Protein-beta; D002273:Carcinogens; D005663:Furans; D018836:Inflammation Mediators; D018942:Macrolides; D016328:NF-kappa B; C513095:inotilone; D015127:9,10-Dimethyl-1,2-benzanthracene; D051546:Cyclooxygenase 2; D013755:Tetradecanoylphorbol Acetate