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Inotilone suppresses phorbol ester-induced inflammation and tumor promotion in mouse skin
Yu-Ching Kuo1, Ching-Shu Lai, Chen-Yu Tsai
1Department of Food Science, Rutgers University, New Brunswick, NJ, USA.
Scope:
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.
Methods And 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.
Conclusion:
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.
Insights
Inotilone, derived from Inonotus mushroom, effectively reduces skin inflammation and prevents tumor development by inhibiting key inflammatory pathways. This natural compound shows promise as a chemopreventive agent for skin cancer.
Area of Science:
- Biochemistry
- Pharmacology
- Oncology
Background:
- Chronic inflammation is a key factor in cancer development.
- Inotilone, found in Inonotus mushroom, possesses known in vitro anti-inflammatory properties.
- Chemoprevention strategies are crucial for reducing cancer risk.
Purpose of the Study:
- To investigate the anti-inflammatory and anti-tumor promotion effects of inotilone on mouse skin.
- To elucidate the molecular mechanisms underlying inotilone's action.
- To evaluate inotilone's potential as a chemopreventive agent.
Main Methods:
- Topical application of inotilone before 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment in mice.
- Assessment of inflammatory mediator production and molecular targets including nuclear factor-kappa B (NF-κB) and CCAAT/enhancer binding protein beta (C/EBPβ).
- Utilizing a two-stage mouse skin carcinogenesis model initiated with 7,12-dimethylbenz[a]anthracene (DMBA) and promoted by TPA.
Main Results:
- Inotilone significantly inhibited TPA-induced acute inflammation.
- Inotilone suppressed NF-κB activation and C/EBPβ expression.
- Inotilone reduced tumor incidence and multiplicity in a mouse skin cancer model.
Conclusions:
- Inotilone demonstrates significant potential as a chemopreventive agent.
- It is effective in mitigating chemically induced skin inflammation and tumorigenesis.
- Inotilone may be a valuable therapeutic agent for inflammatory conditions and epithelial skin cancers.
