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Pharmacologic Induction of Epidermal Melanin and Protection Against Sunburn in a Humanized Mouse Model
Published on: September 7, 2013
Tangeretin reduces ultraviolet B (UVB)-induced cyclooxygenase-2 expression in mouse epidermal cells by blocking
Ji Hye Yoon1, Tae-Gyu Lim, Kyung Mi Lee
1Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul, Republic of Korea.
Abstract:
The present study examined the effects of tangeretin, a polymethoxylated flavonone present in citrus fruits, on ultraviolet B (UVB)-induced cyclooxygenase-2 (COX-2) expression in JB6 P+ mouse skin epidermal cells. Tangeretin suppressed UVB-induced COX-2 expression and transactivation of nuclear factor-κB and activator protein-1 in JB6 P+ cells. Moreover, tangeretin blocked UVB-induced phosphorylation of Akt and mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated protein kinase, c-Jun N-terminal kinase, and p38, and attenuated the phosphorylation of MAPK kinases 1/2, 3/6, and 4. Tangeretin also limited the endogenous generation of reactive oxygen species (ROS), thereby protecting the cells against oxidative stress. However, tangeretin did not scavenge the stable 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and influence the nicotinamide adenine dinucleotide phosphate oxidase activity. These results suggest that the anti-inflammatory effects of tangeretin stem from its modulation of cell signaling and suppression of intracellular ROS generation. Tangeretin may have a potent chemopreventive effect in skin cancer.
Insights
Tangeretin, a citrus flavonoid, reduces inflammation by inhibiting key cell signaling pathways and decreasing reactive oxygen species (ROS) in skin cells. This suggests tangeretin may offer chemopreventive benefits against skin cancer.
Area of Science:
- Biochemistry
- Molecular Biology
- Dermatology
Background:
- Ultraviolet B (UVB) radiation is a known carcinogen that induces inflammatory responses in skin.
- Cyclooxygenase-2 (COX-2) is a key enzyme in inflammation and cancer development.
- Flavonoids, like tangeretin found in citrus fruits, possess potential anti-inflammatory and anti-cancer properties.
Purpose of the Study:
- To investigate the effects of tangeretin on UVB-induced COX-2 expression in mouse skin epidermal cells.
- To elucidate the molecular mechanisms underlying tangeretin's anti-inflammatory actions.
- To assess tangeretin's potential as a chemopreventive agent for skin cancer.
Main Methods:
- JB6 P+ mouse skin epidermal cells were treated with tangeretin and exposed to UVB radiation.
- Expression of COX-2, nuclear factor-κB (NF-κB), and activator protein-1 (AP-1) was analyzed.
- Phosphorylation of Akt and mitogen-activated protein kinases (MAPKs) was assessed.
- Reactive oxygen species (ROS) generation was measured.
Main Results:
- Tangeretin significantly suppressed UVB-induced COX-2 expression and the activation of NF-κB and AP-1.
- Tangeretin inhibited the phosphorylation of Akt and various MAPKs (ERK, JNK, p38) and their upstream kinases.
- Tangeretin reduced intracellular ROS generation, protecting cells from oxidative stress, but did not directly scavenge DPPH radicals or inhibit NADPH oxidase activity.
Conclusions:
- Tangeretin exerts anti-inflammatory effects by modulating cell signaling pathways and reducing intracellular ROS production.
- These findings suggest tangeretin has potential chemopreventive properties against skin cancer.
- Tangeretin's mechanism involves inhibiting key inflammatory mediators and signaling cascades activated by UVB radiation.
